Skip to main content

Wie Antigene den T-Lymphocyten präsentiert werden

  • Chapter
  • First Online:
Janeway Immunologie

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Kenneth Murphy .

Appendices

Aufgaben

1 6.1 Kurze Antwort

Dendritische Zellen können exogene Antigene effizient aufnehmen und den T-Zellen auf MHC-Klasse-I-Molekülen präsentieren. Wie unterscheiden sie sich dadurch von allen anderen Körperzellen und warum ist das von Bedeutung?

1 6.2 Bitte zuordnen

Welcher Begriff gehört zu welcher Beschreibung?

A.

Proteasom

i.

verdrängt die konstitutiven β-Untereinheiten der katalytischen Kammer als Reaktion auf Interferone

B.

20S-Core-Komplex

ii.

besteht aus einem katalytischen Core-Komplex und zwei regulatorischen 19S-Cap-Komplexen

C.

LMP2, LMP7, MECL-1

iii.

großer zylindrischer Komplex aus 28 Untereinheiten, die in vier gestapelten Ringen angeordnet sind

D.

PA28

iv.

markiert Proteine für den Abbau

E.

Lysin-48-Ubiquitin

v.

bindet an das Proteasom und erhöht die Freisetzungsrate der Peptide aus dem Proteasom

1 6.3 Richtig oder falsch

Die Oberflächenexpression von MHC-Klasse-I-Molekülen wird von der Transportkapazität der Zelle für Peptide in das endoplasmatische Reticulum nicht beeinflusst.

1 6.4 Bitte ergänzen

Polypeptide, die für die Zellmembran bestimmt sind, werden in das Lumen des endoplasmatischen Reticulums transloziert, was jedoch verwirrend ist, da die von MHC-Klasse-Molekülen-I präsentierten Peptide im ________ vorkommen. Weitere Untersuchungen zeigten, dass die Präsentation der cytosolischen Peptide von einer Familie von ABC-Transportproteinen (________) ermöglicht wird, die den ATP-abhängigen Transport von Peptiden in das Lumen des ________ bewerkstelligen. Dieser Transporterkomplex besitzt nur eine begrenzte Spezifität für die transportierten Peptide; so sind beispielsweise die Peptide im Allgemeinen ________ Aminosäuren lang und der Transport wird bei ________ Resten im Carboxyterminus begünstigt und bei ________ Resten in den ersten ________ aminoterminalen Aminosäuren gehemmt.

1 6.5 Multiple Choice

Dendritische CD8-Zellen besitzen die besondere Eigenschaft, Antigene sehr effektiv in Form einer Kreuzpräsentation darzubieten. Welche der folgenden Kombinationen beinhaltet einen Transkriptionsfaktor, der für die Entwicklung der dendritischen CD8-Zellen essenziell ist, und einen nur von diesen Zellen exprimierten Oberflächenmarker?

  1. A.

    CIITA, CD74

  2. B.

    BATF3, CD4

  3. C.

    CIITA, CD94

  4. D.

    BATF3, XCR1

1 6.6 Bitte zuordnen

Welcher Begriff gehört zu welcher Beschreibung?

A.

TRIC

i.

hält die α-Kette der MHC-Klasse-I-Moleküle in einem teilweise gefalteten Zustand

B.

ERAAP

ii.

schützt Peptide, die im Cytosol erzeugt werden, vor einem vollständigen Abbau

C.

Calnexin

iii.

bildet eine Brücke zwischen dem MHC-Klasse-I-Molekül und dem TAP-Komplex

D.

ERp57

iv.

verkürzt den Aminoterminus von Peptiden, die für eine Bindung durch MHC zu lang sind

E.

Tapasin

v.

öffnet und schließt während der Peptidbeladung Disulfidbrücken in der MHC-Klasse-I-α-Domäne

1 6.7 Richtig oder falsch

MHC-Klasse-II-Moleküle präsentieren keine cytosolischen Antigene.

1 6.8 Bitte zuordnen

In welcher Reihenfolge geht die MHC-Klasse-II-Prozessierung in einer antigenpräsentierenden Zelle vor sich?

_____ Abspaltung der Trimerisierungsdomäne CD74

_____ Translokation des MHC-Klasse-II-Moleküls in das endoplasmatische Reticulum

_____ Cathepsin S spaltet LIP22 und das CLIP-Fragment verbleibt auf dem MHC-Molekül

_____ CD74-Trimere binden nichtkovalent an MHC-Klasse-II-α:β-Heterodimere

_____ HLA-DM katalysiert die Freisetzung von CLIP und stimuliert das Peptid-Editing

_____ Calnexin setzt MHC-Klasse-II-Heterodimere für den Transport zu einem endosomalen Kompartiment mit niedrigem pH-Wert frei

1 6.9 Multiple Choice

Bei welchem der folgenden Proteine führt eine Funktionsstörung dazu, dass kein Priming von CD8-T-Zellen mehr möglich ist?

  1. A.

    HLA-DM

  2. B.

    Cathepsin S

  3. C.

    TAP1/2

  4. D.

    CD74

1 6.10 Multiple Choice

Eine Funktionsstörung in welchem der folgenden Proteine führt dazu, dass die Präsentation cytosolischer Peptide durch MHC-Klasse-II-Moleküle reduziert ist?

  1. A.

    IRGM3

  2. B.

    BATF3

  3. C.

    MARCH-1

  4. D.

    TAP1/2

1 6.11 Richtig oder falsch

Superantigene induzieren keine adaptive Immunantwort und wirken unabhängig von peptidspezifischen MHC-TCR-Wechselwirkungen?

1 6.12 Multiple Choice

Welche der folgenden Aussagen ist falsch?

  1. A.

    Polymorphismen an jedem Locus können potenziell die Anzahl der verschiedenen MHC-Moleküle verdoppeln, die ein Individuum exprimieren kann.

  2. B.

    Pathogene können dem Immunsystem entkommen, indem das immundominante Epitop mutiert, wodurch die Affinität des zugehörigen MHC-Allel-Produkts verlorengeht.

  3. C.

    Pathogene verursachen keinen Evolutionsdruck zur Selektion von MHC-Allelen, die einen Schutz gegenüber diesen Pathogenen bewirken.

  4. D.

    Die DRα-Kette und das homologe Protein der Maus Eα sind monomorph.

1 6.13 Richtig oder falsch

Klassische MHC-Klasse-I-Moleküle sind hochgradig polymorph, während MHC-Klasse-Ib-Moleküle oligomorph sind.

1 6.14 Bitte zuordnen

Welche Beschreibung gehört zu welchem MHC-Klasse-Ib-Molekül?

A.

H2-M3

i.

präsentiert mikrobielle Folsäuremetaboliten

B.

MIC-A

ii.

bindet α-GalCer

C.

CD1d

iii.

präsentiert N-formylierte Peptide

D.

MR1

iv.

bindet NKG2D

Literatur

1.1 Allgemeine Literatur

  • ■ Germain, R.N.: MHC-dependent antigen processing and peptide presentation: providing ligands for T lymphocyte activation. Cell 1994, 76:287–299.

  • ■ Klein, J.: Natural History of the Major Histocompatibility Complex. New York: Wiley, 1986.

  • ■ Moller, G. (ed.): Origin of major histocompatibility complex diversity. Immunol. Rev. 1995, 143:5–292.

  • ■ Trombetta, E.S. and Mellman, I.: Cell biology of antigen processing in vitro and in vivo. Annu. Rev. Immunol. 2005, 23:975–1028.

1.2 Literatur zu den einzelnen Abschnitten

1.2.1 Abschnitt 6.1.1

  • ■ Guermonprez, P., Valladeau, J., Zitvogel, L., Théry, C., and Amigorena, S.: Antigen presentation and T cell stimulation by dendritic cells. Annu. Rev. Immunol. 2002, 20:621–667.

  • ■ Lee, H.K., Mattei, L.M., Steinberg, B.E., Alberts, P., Lee, Y.H., Chervonsky, A., Mizushima, N., Grinstein, S., and Iwasaki, A.: In vivo requirement for Atg5 in antigen presentation by dendritic cells. Immunity 2010, 32:227–239.

  • ■ Segura, E. and Villadangos, J.A.: Antigen presentation by dendritic cells in vivo. Curr. Opin. Immunol. 2009, 21:105–110.

  • ■ Vyas, J.M., Van der Veen, A.G., and Ploegh, H.L.: The known unknowns of anti-gen processing and presentation. Nat. Rev. Immunol. 2008, 8:607–618.

1.2.2 Abschnitt 6.1.2

  • ■ Basler, M., Kirk. C.J., and Groettrup, M.: The immunoproteasome in antigen processing and other immunological functions. Curr. Opin. Immunol. 2013, 25:74–80.

  • ■ Brocke, P., Garbi, N., Momburg, F., and Hammerling, G.J.: HLA-DM, HLA-DO and tapasin: functional similarities and differences. Curr. Opin. Immunol. 2002, 14:22–29.

  • ■ Cascio, P., Call, M., Petre, B.M., Walz, T., and Goldberg, A.L.: Properties of the hybrid form of the 26S proteasome containing both 19S and PA28 complexes. EMBO J. 2002, 21:2636–2645.

  • ■ Gromme, M. and Neefjes, J.: Antigen degradation or presentation by MHC class I molecules via classical and non-classical pathways. Mol. Immunol. 2002, 39:181–202.

  • ■ Goldberg, A.L., Cascio, P., Saric, T., and Rock, K.L.: The importance of the proteasome and subsequent proteolytic steps in the generation of antigenic peptides. Mol. Immunol. 2002, 39:147–164.

  • ■ Hammer, G.E., Gonzalez, F., Champsaur, M., Cado, D., and Shastri, N.: The aminopeptidase ERAAP shapes the peptide repertoire displayed by major histocompatibility complex class I molecules. Nat. Immunol. 2006, 7:103–112.

  • ■ Hammer, G.E., Gonzalez, F., James, E., Nolla, H., and Shastri, N.: In the absence of aminopeptidase ERAAP, MHC class I molecules present many unstable and highly immunogenic peptides. Nat. Immunol. 2007, 8:101–108.

  • ■ Murata, S., Sasaki, K., Kishimoto, T., Niwa, S., Hayashi, H., Takahama, Y., and Tanaka, K.: Regulation of CD8+ T cell development by thymus-specific proteasomes. Science 2007, 316:1349–1353.

  • ■ Schubert, U., Anton, L.C., Gibbs, J., Norbury, C.C., Yewdell, J.W., and Bennink, J.R.: Rapid degradation of a large fraction of newly synthesized proteins by proteasomes. Nature 2000, 404:770–774.

  • ■ Serwold, T., Gonzalez, F., Kim, J., Jacob, R., and Shastri, N.: ERAAP customizes peptides for MHC class I molecules in the endoplasmic reticulum. Nature 2002, 419:480–483.

  • ■ Shastri, N., Schwab, S., and Serwold, T.: Producing nature’s gene-chips: the generation of peptides for display by MHC class I molecules. Annu. Rev. Immunol. 2002, 20:463–493.

  • ■ Sijts, A., Sun, Y., Janek, K., Kral, S., Paschen, A., Schadendorf, D., and Kloetzel, P.M.: The role of the proteasome activator PA28 in MHC class I antigen processing. Mol. Immunol. 2002, 39:165–169.

  • ■ Vigneron, N., Stroobant, V., Chapiro, J., Ooms, A., Degiovanni, G., Morel, S., van der Bruggen, P., Boon, T., and Van den Eynde, B.J.: An antigenic peptide produced by peptide splicing in the proteasome. Science 2004, 304:587–590.

  • ■ Villadangos, J.A.: Presentation of antigens by MHC class II molecules: getting the most out of them. Mol. Immunol. 2001, 38:329–346.

  • ■ Williams, A., Peh, C.A., and Elliott, T.: The cell biology of MHC class I antigen presentation. Tissue Antigens 2002, 59:3–17.

1.2.3 Abschnitt 6.1.3

  • ■ Gorbulev, S., Abele, R., and Tampe, R.: Allosteric crosstalk between peptide-binding, transport, and ATP hydrolysis of the ABC transporter TAP. Proc. Natl Acad. Sci. USA 2001, 98:3732–3737.

  • ■ Kelly, A., Powis, S.H., Kerr, L.A., Mockridge, I., Elliott, T., Bastin, J., Uchanska-Ziegler, B., Ziegler, A., Trowsdale, J., and Townsend, A.: Assembly and function of the two ABC transporter proteins encoded in the human major histocompatibility complex. Nature 1992, 355:641–644.

  • ■ Lankat-Buttgereit, B. and Tampe, R.: The transporter associated with anti-gen processing: function and implications in human diseases. Physiol. Rev. 2002, 82:187–204.

  • ■ Powis, S.J., Townsend, A.R., Deverson, E. V., Bastin, J., Butcher, G.W., and Howard, J.C.: Restoration of antigen presentation to the mutant cell line RMA-S by an MHC-linked transporter. Nature 1991, 354:528–531.

  • ■ Townsend, A., Ohlen, C., Foster, L., Bastin, J., Lunggren, H.G., and Karre, K.: A mutant cell in which association of class I heavy and light chains is induced by viral peptides. Cold Spring Harbor Symp. Quant. Biol. 1989, 54:299–308.

1.2.4 Abschnitt 6.1.4

  • ■ Bouvier, M.: Accessory proteins and the assembly of human class I MHC molecules: a molecular and structural perspective. Mol. Immunol. 2003, 39:697–706.

  • ■ Gao, B., Adhikari, R., Howarth, M., Nakamura, K., Gold, M.C., Hill, A.B., Knee, R., Michalak, M., and Elliott, T.: Assembly and antigen-presenting function of MHC class I molecules in cells lacking the ER chaperone calreticulin. Immunity 2002, 16:99–109.

  • ■ Grandea III, A.G. and Van Kaer, L.: Tapasin: an ER chaperone that controls MHC class I assembly with peptide. Trends Immunol. 2001, 22:194–199.

  • ■ Van Kaer, L.: Accessory proteins that control the assembly of MHC molecules with peptides. Immunol. Res. 2001, 23:205–214.

  • ■ Williams, A., Peh, C.A., and Elliott, T.: The cell biology of MHC class I antigen presentation. Tissue Antigens 2002, 59:3–17.

  • ■ Williams, A.P., Peh, C.A., Purcell, A.W., McCluskey, J., and Elliott, T.: Optimization of the MHC class I peptide cargo is dependent on tapasin. Immunity 2002, 16:509–520.

  • ■ Zhang, W., Wearsch, P.A., Zhu, Y., Leonhardt, R.M., and Cresswell P.: A role for UDP-glucose glycoprotein glucosyltransferase in expression and quality control of MHC class I molecules. Proc. Natl Acad. Sci. USA 2011, 108:4956–4961.

1.2.5 Abschnitt 6.1.5

  • ■ Ackerman, A.L. and Cresswell, P.: Cellular mechanisms governing cross-presentation of exogenous antigens. Nat. Immunol. 2004, 5:678–684.

  • ■ Bevan, M.J.: Minor H antigens introduced on H-2 different stimulating cells cross-react at the cytotoxic T cell level during in vivo priming. J. Immunol. 1976, 117:2233–2238.

  • ■ Bevan, M.J.: Helping the CD8+ T cell response. Nat. Rev. Immunol. 2004, 4:595–602.

  • ■ Hildner, K., Edelson, B.T., Purtha, W.E., Diamond, M., Matsushita, H., Kohyama, M., Calderon, B., Schraml, B.U., Unanue, E.R., Diamond, M.S., et al.: Batf3 deficiency reveals a critical role for CD8α+ dendritic cells in cytotoxic T cell immunity. Science 2008, 322:1097–1100.

  • ■ Segura, E. and Villadangos, J.A.: A modular and combinatorial view of the antigen cross-presentation pathway in dendritic cells. Traffic 2011, 12:1677–1685.

1.2.6 Abschnitt 6.1.6

  • ■ Dengjel, J., Schoor, O., Fischer, R., Reich, M., Kraus, M., Müller, M., Kreymborg, K., Altenberend, F., Brandenburg, J., Kalbacher, H., et al.: Autophagy promotes MHC class II presentation of peptides from intracellular source proteins. Proc. Natl Acad. Sci. USA 2005, 102:7922–7927.

  • ■ Deretic, V., Saitoh, T., and Akira, S.: Autophagy in infection, inflammation and immunity. Nat. Rev. Immunol. 2013, 13:722–737.

  • ■ Godkin, A.J., Smith, K.J., Willis, A., Tejada-Simon, M.V., Zhang, J., Elliott, T., and Hill, A.V.: Naturally processed HLA class II peptides reveal highly conserved immunogenic flanking region sequence preferences that reflect antigen processing rather than peptide–MHC interactions. J. Immunol. 2001, 166:6720–6727.

  • ■ Hiltbold, E.M. and Roche, P.A.: Trafficking of MHC class II molecules in the late secretory pathway. Curr. Opin. Immunol. 2002, 14:30–35.

  • ■ Hsieh, C.S., deRoos, P., Honey, K., Beers, C., and Rudensky, A.Y.: A role for cathepsin L and cathepsin S in peptide generation for MHC class II presentation. J. Immunol. 2002, 168:2618–2625.

  • ■ Lennon-Duménil, A.M., Bakker, A.H., Wolf-Bryant, P., Ploegh, H.L., and Lagaudrière-Gesbert, C.: A closer look at proteolysis and MHC-class-II-restricted antigen presentation. Curr. Opin. Immunol. 2002, 14:15–21.

  • ■ Li, P., Gregg, J.L., Wang, N., Zhou, D., O’Donnell, P., Blum, J.S., and Crotzer, V.L.: Compartmentalization of class II antigen presentation: contribution of cytoplasmic and endosomal processing. Immunol. Rev. 2005, 207:206–217.

  • ■ Maric, M., Arunachalam, B., Phan, U.T., Dong, C., Garrett, W.S., Cannon, K.S., Alfonso, C., Karlsson, L., Flavell, R.A., and Cresswell, P.: Defective antigen processing in GILT-free mice. Science 2001, 294:1361–1365.

  • ■ Münz, C.: Enhancing immunity through autophagy. Annu. Rev. Immunol. 2009, 27:423–449.

  • ■ Pluger, E.B., Boes, M., Alfonso, C., Schroter, C.J., Kalbacher, H., Ploegh, H.L., and Driessen, C.: Specific role for cathepsin S in the generation of antigenic peptides in vivo. Eur. J. Immunol. 2002, 32:467–476.

1.2.7 Abschnitt 6.1.7

  • ■ Gregers, T.F., Nordeng, T.W., Birkeland, H.C., Sandlie, I., and Bakke, O.: The cytoplasmic tail of invariant chain modulates antigen processing and presentation. Eur. J. Immunol. 2003, 33:277–286.

  • ■ Hiltbold, E.M. and Roche, P.A.: Trafficking of MHC class II molecules in the late secretory pathway. Curr. Opin. Immunol. 2002, 14:30–35.

  • ■ Kleijmeer, M., Ramm, G., Schuurhuis, D., Griffith, J., Rescigno, M., Ricciardi-Castagnoli, P., Rudensky, A.Y., Ossendorp, F., Melief, C.J., Stoorvogel, W., et al.: Reorganization of multivesicular bodies regulates MHC class II antigen presentation by dendritic cells. J. Cell Biol. 2001, 155:53–63.

  • ■ van Lith, M., van Ham, M., Griekspoor, A., Tjin, E., Verwoerd, D., Calafat, J., Janssen, H., Reits, E., Pastoors, L., and Neefjes, J.: Regulation of MHC class II antigen presentation by sorting of recycling HLA-DM/DO and class II within the multivesicular body. J. Immunol. 2001, 167:884–892.

1.2.8 Abschnitt 6.1.8

  • ■ Alfonso, C. and Karlsson, L.: Nonclassical MHC class II molecules. Annu. Rev. Immunol. 2000, 18:113–142.

  • ■ Apostolopoulos, V., McKenzie, I.F., and Wilson, I. A.: Getting into the groove: unusual features of peptide binding to MHC class I molecules and implications in vaccine design. Front. Biosci. 2001, 6:D1311–D1320.

  • ■ Buslepp, J., Zhao, R., Donnini, D., Loftus, D., Saad, M., Appella, E., and Collins, E.J.: T cell activity correlates with oligomeric peptide-major histocompatibility complex binding on T cell surface. J. Biol. Chem. 2001, 276:47320–47328.

  • ■ Gu, Y., Jensen, P.E., and Chen, X.: Immunodeficiency and autoimmunity in H2-O-deficient mice. J. Immunol. 2013, 190:126–137.

  • ■ Hill, J.A., Wang, D., Jevnikar, A.M., Cairns, E., and Bell, D.A.: The relationship between predicted peptide-MHC class II affinity and T-cell activation in a HLA-DRβ1*0401 transgenic mouse model. Arthritis Res. Ther. 2003, 5:R40–R48.

  • ■ Mellins, E.D. and Stern, L.J.: HLA-DM and HLA-DO, key regulators of MHC-II processing and presentation. Curr. Opin. Immunol. 2014, 26:115–122.

  • ■ Nelson, C.A., Vidavsky, I., Viner, N.J., Gross, M.L., and Unanue, E.R.: Amino-terminal trimming of peptides for presentation on major histocompatibility complex class II molecules. Proc. Natl Acad. Sci. USA 1997, 94:628–633.

  • ■ Pathak, S.S., Lich, J.D., and Blum, J.S.: Cutting edge: editing of recycling class II:peptide complexes by HLA-DM. J. Immunol. 2001, 167:632–635.

  • ■ Pos, W., Sethi, D.K., Call, M.J., Schulze, M.S., Anders, A.K., Pyrdol, J., and Wucherpfennig, K.W.: Crystal structure of the HLA-DM-HLA-DR1 complex defines mechanisms for rapid peptide selection. Cell 2012, 151:1557–1568.

  • ■ Qi, L. and Ostrand-Rosenberg, S.: H2-O inhibits presentation of bacterial superantigens, but not endogenous self antigens. J. Immunol. 2001, 167:1371–1378.

  • ■ Su, R.C. and Miller, R.G.: Stability of surface H-2Kb, H-2Db, and peptide-receptive H-2Kb on splenocytes. J. Immunol. 2001, 167:4869–4877.

  • ■ Zarutskie, J.A., Busch, R., Zavala-Ruiz, Z., Rushe, M., Mellins, E.D., and Stern, L.J.: The kinetic basis of peptide exchange catalysis by HLA-DM. Proc. Natl Acad. Sci. USA 2001, 98:12450–12455.

1.2.9 Abschnitt 6.1.9

  • ■ Baravalle, G., Park, H., McSweeney, M., Ohmura-Hoshino, M., Matsuki, Y., Ishido, S., and Shin, J.S.: Ubiquitination of CD86 is a key mechanism in regulating anti-gen presentation by dendritic cells. J. Immunol. 2011, 187:2966–2973.

  • ■ De Gassart, A., Camosseto, V., Thibodeau, J., Ceppi, M., Catalan, N., Pierre, P., and Gatti, E.: MHC class II stabilization at the surface of human dendritic cells is the result of maturation-dependent MARCH I down-regulation. Proc. Natl Acad. Sci. USA 2008, 105:3491–3496.

  • ■ Jiang, X. and Chen, Z.J.: The role of ubiquitylation in immune defence and pathogen evasion. Nat. Rev. Immunol. 2012, 12:35–48.

  • ■ Ma, J.K., Platt, M.Y., Eastham-Anderson, J., Shin, J.S., and Mellman, I.: MHC class II distribution in dendritic cells and B cells is determined by ubiquitin chain length. Proc. Natl Acad. Sci. USA 2012, 109:8820–8827.

  • ■ Ohmura-Hoshino, M., Matsuki, Y., Mito-Yoshida, M., Goto, E., Aoki-Kawasumi, M., Nakayama, M., Ohara, O., and Ishido, S.: Cutting edge: requirement of MARCH-I-mediated MHC II ubiquitination for the maintenance of conventional dendritic cells. J. Immunol. 2009, 183:6893–6897.

  • ■ Walseng, E., Furuta, K., Bosch, B., Weih, K. A., Matsuki, Y., Bakke, O., Ishido, S., and Roche, P.A.: Ubiquitination regulates MHC class II-peptide complex retention and degradation in dendritic cells. Proc. Natl Acad. Sci. USA 2010, 107:20465–20470.

1.2.10 Abschnitt 6.2.1

  • ■ Aguado, B., Bahram, S., Beck, S., Campbell, R.D., Forbes, S.A., Geraghty, D., Guillaudeux, T., Hood, L., Horton, R., Inoko, H., et al. (the MHC Sequencing Consortium): Complete sequence and gene map of a human major histocom-patibility complex. Nature 1999, 401:921–923.

  • ■ Chang, C.H., Gourley, T.S., and Sisk, T.J.: Function and regulation of class II transactivator in the immune system. Immunol. Res. 2002, 25:131–142.

  • ■ Kumnovics, A., Takada, T., and Lindahl, K.F.: Genomic organization of the mammalian MHC. Annu. Rev. Immunol. 2003, 21:629–657.

  • ■ Lefranc, M.P.: IMGT, the international ImMunoGeneTics database. Nucleic Acids Res. 2003, 31:307–310.

1.2.11 Abschnitt 6.2.2

  • ■ Gaur, L.K. and Nepom, G.T.: Ancestral major histocompatibility complex DRB genes beget conserved patterns of localized polymorphisms. Proc. Natl Acad. Sci. USA 1996, 93:5380–5383.

  • ■ Marsh, S.G.: Nomenclature for factors of the HLA system, update December 2002. Eur. J. Immunogenet. 2003, 30:167–169.

  • ■ Robinson, J. and Marsh, S.G.: HLA informatics. Accessing HLA sequences from sequence databases. Methods Mol. Biol. 2003, 210:3–21.

1.2.12 Abschnitt 6.2.3

  • ■ Falk, K., Rotzschke, O., Stevanovic, S., Jung, G., and Rammensee, H.G.: Allele-specific motifs revealed by sequencing of self-peptides eluted from MHC molecules. Nature 1991, 351:290–296.

  • ■ Garcia, K.C., Degano, M., Speir, J.A., and Wilson, I. A.: Emerging principles for T cell receptor recognition of antigen in cellular immunity. Rev. Immunogenet. 1999, 1:75–90.

  • ■ Katz, D.H., Hamaoka, T., Dorf, M. E., Maurer, P.H., and Benacerraf, B.: Cell interactions between histoincompatible T and B lymphocytes. IV. Involvement of immune response (Ir) gene control of lymphocyte interaction controlled by the gene. J. Exp. Med. 1973, 138:734–739.

  • ■ Kjer-Nielsen, L., Clements, C.S., Brooks, A.G., Purcell, A.W., Fontes, M.R., McCluskey, J., and Rossjohn, J.: The structure of HLA-B8 complexed to an immunodominant viral determinant: peptide-induced conformational changes and a mode of MHC class I dimerization. J. Immunol. 2002, 169:5153–5160.

  • ■ Wang, J.H. and Reinherz, E.L.: Structural basis of T cell recognition of peptides bound to MHC molecules. Mol. Immunol. 2002, 38:1039–1049.

  • ■ Zinkernagel, R.M. and Doherty, P.C.: Restriction of in vivo T-cell mediated cytotoxicity in lymphocytic choriomeningitis within a syngeneic or semiallogeneic system. Nature 1974, 248:701–702.

1.2.13 Abschnitt 6.2.4

  • ■ Felix, N.J. and Allen, P.M.: Specificity of T-cell alloreactivity. Nat. Rev. Immunol. 2007, 7:942–953.

  • ■ Feng, D., Bond, C.J., Ely, L.K., Maynard, J., and Garcia, K.C.: Structural evidence for a germline-encoded T cell receptor–major histocompatibility complex interaction ‘codon.’ Nat. Immunol. 2007, 8:975–993.

  • ■ Hennecke, J. and Wiley, D.C.: Structure of a complex of the human α/β T cell receptor (TCR) HA1.7, influenza hemagglutinin peptide, and major histocom-patibility complex class II molecule, HLA-DR4 (DRA*0101 and DRB1*0401): insight into TCR cross-restriction and alloreactivity. J. Exp. Med. 2002, 195:571–581.

  • ■ Jankovic, V., Remus, K., Molano, A., and Nikolich-Zugich, J.: T cell recognition of an engineered MHC class I molecule: implications for peptide-independent alloreactivity. J. Immunol. 2002, 169:1887–1892.

  • ■ Nesic, D., Maric, M., Santori, F.R., and Vukmanovic, S.: Factors influencing the patterns of T lymphocyte allorecognition. Transplantation 2002, 73:797–803.

  • ■ Reiser, J.B., Darnault, C., Guimezanes, A., Gregoire, C., Mosser, T., Schmitt-Verhulst, A.M., Fontecilla-Camps, J.C., Malissen, B., Housset, D., and Mazza, G.: Crystal structure of a T cell receptor bound to an allogeneic MHC molecule. Nat. Immunol. 2000, 1:291–297.

  • ■ Rötzschke, O., Falk, K., Faath, S., Rammensee, H.G.: On the nature of peptides involved in T cell alloreactivity. J. Exp. Med. 1991, 174:1059–1071.

  • ■ Speir, J.A., Garcia, K.C., Brunmark, A., Degano, M., Peterson, P.A., Teyton, L., and Wilson, I. A.: Structural basis of 2C TCR allorecognition of H-2Ld peptide complexes. Immunity 1998, 8:553–562.

1.2.14 Abschnitt 6.2.5

  • ■ Acha-Orbea, H., Finke, D., Attinger, A., Schmid, S., Wehrli, N., Vacheron, S., Xenarios, I., Scarpellino, L., Toellner, K.M., MacLennan, I.C., et al.: Interplays between mouse mammary tumor virus and the cellular and humoral immune response. Immunol. Rev. 1999, 168:287–303.

  • ■ Kappler, J.W., Staerz, U., White, J., and Marrack, P.: T cell receptor Vb elements which recognize Mls-modified products of the major histocompatibility complex. Nature 1988, 332:35–40.

  • ■ Rammensee, H.G., Kroschewski, R., and Frangoulis, B.: Clonal anergy induced in mature Vβ6+ T lymphocytes on immunizing Mls-1b mice with Mls-1a expressing cells. Nature 1989, 339:541–544.

  • ■ Spaulding, A.R., Salgado-Pabón, W., Kohler, P.L., Horswill, A.R., Leung, D.Y., and Schlievert, P.M.: Staphylococcal and streptococcal superantigen exotoxins. Clin. Microbiol. Rev. 2013, 26:422–447.

  • ■ Sundberg, E.J., Li, H., Llera, A.S., McCormick, J.K., Tormo, J., Schlievert, P.M., Karjalainen, K., and Mariuzza, R.A.: Structures of two streptococcal superantigens bound to TCR β chains reveal diversity in the architecture of T cell signaling complexes. Structure 2002, 10:687–699.

  • ■ Torres, B.A., Perrin, G.Q., Mujtaba, M.G., Subramaniam, P.S., Anderson, A.K., and Johnson, H.M.: Superantigen enhancement of specific immunity: antibody production and signaling pathways. J. Immunol. 2002, 169:2907–2914.

  • ■ White, J., Herman, A., Pullen, A.M., Kubo, R., Kappler, J.W., and Marrack, P.: The Vβ-specific super antigen staphylococcal enterotoxin B: stimulation of mature T cells and clonal deletion in neonatal mice. Cell 1989, 56:27–35.

1.2.15 Abschnitt 6.2.6

  • ■ Hill, A.V., Elvin, J., Willis, A.C., Aidoo, M., Allsopp, C.E.M., Gotch, F.M., Gao, X.M., Takiguchi, M., Greenwood, B.M., Townsend, A.R.M., et al.: Molecular anal-ysis of the association of B53 and resistance to severe malaria. Nature 1992, 360:435–440.

  • ■ Martin, M.P. and Carrington, M.: Immunogenetics of viral infections. Curr. Opin. Immunol. 2005, 17:510–516.

  • ■ Messaoudi, I., Guevara Patino, J.A., Dyall, R., LeMaoult, J., and Nikolich-Zugich, J.: Direct link between mhc polymorphism, T cell avidity, and diversity in immune defense. Science 2002, 298:1797–1800.

  • ■ Potts, W.K. and Slev, P.R.: Pathogen-based models favouring MHC genetic diversity. Immunol. Rev. 1995, 143:181–197.

1.2.16 Abschnitt 6.3.1

  • ■ Alfonso, C. and Karlsson, L.: Nonclassical MHC class II molecules. Annu. Rev. Immunol. 2000, 18:113–142.

  • ■ Hofstetter, A.R., Sullivan, L.C., Lukacher, A.E., and Brooks, A.G..: Diverse roles of non-diverse molecules: MHC class Ib molecules in host defense and control of autoimmunity. Curr. Opin. Immunol. 2011, 23:104–110.

  • ■ Loconto, J., Papes, F., Chang, E., Stowers, L., Jones, E.P., Takada, T., Kumánovics, A., Fischer Lindahl, K., and Dulac, C.: Functional expression of murine V2R pheromone receptors involves selective association with the M10 and M1 families of MHC class Ib molecules. Cell 2003, 112:607–118.

  • ■ Powell, L.W., Subramaniam, V.N., and Yapp, T.R.: Haemochromatosis in the new millennium. J. Hepatol. 2000, 32:48–62.

1.2.17 Abschnitt 6.3.2

  • ■ Borrego, F., Kabat, J., Kim, D.K., Lieto, L., Maasho, K., Pena, J., Solana, R., and Coligan, J.E.: Structure and function of major histocompatibility complex (MHC) class I specific receptors expressed on human natural killer (NK) cells. Mol. Immunol. 2002, 38:637–660.

  • ■ Boyington, J.C., Riaz, A.N., Patamawenu, A., Coligan, J.E., Brooks, A.G., and Sun, P.D.: Structure of CD94 reveals a novel C-type lectin fold: implications for the NK cell-associated CD94/NKG2 receptors. Immunity 1999, 10:75–82.

  • ■ Braud, V.M., Allan, D.S., O’Callaghan, C.A., Söderström, K., D’Andrea, A., Ogg, G.S., Lazetic, S., Young, N.T., Bell, J.I., Phillips, J.H., et al.: HLA-E binds to natural killer cell receptors CD94/NKG2A, B and C. Nature 1998, 391:795–799.

  • ■ Braud, V.M. and McMichael, A.J.: Regulation of NK cell functions through interaction of the CD94/NKG2 receptors with the nonclassical class I molecule HLA-E. Curr. Top. Microbiol. Immunol. 1999, 244:85–95.

  • ■ Jiang, H., Canfield, S.M., Gallagher, M.P., Jiang, H.H., Jiang, Y., Zheng, Z., and Chess, L.: HLA-E-restricted regulatory CD8(+) T cells are involved in development and control of human autoimmune type 1 diabetes. J. Clin. Invest. 2010, 120:3641–3650.

  • ■ Lanier, L.L.: NK cell recognition. Annu. Rev. Immunol. 2005, 23:225–274.

  • ■ Lopez-Botet, M., and Bellon, T.: Natural killer cell activation and inhibition by receptors for MHC class I. Curr. Opin. Immunol. 1999, 11:301–307.

  • ■ Lopez-Botet, M. Bellon, T., Llano, M., Navarro, F., Garcia, P., and de Miguel, M.: Paired inhibitory and triggering NK cell receptors for HLA class I molecules. Hum. Immunol. 2000, 61:7–17.

  • ■ Lopez-Botet, M., Llano, M., Navarro, F., and Bellon, T.: NK cell recognition of non-classical HLA class I molecules. Semin. Immunol. 2000, 12:109–119.

  • ■ Lu, L., Ikizawa, K., Hu, D., Werneck, M.B., Wucherpfennig, K.W., and Cantor, H.: Regulation of activated CD4+ T cells by NK cells via the Qa-1-NKG2A inhibitory pathway. Immunity 2007, 26:593–604.

  • ■ Pietra, G., Romagnani, C., Moretta, L., and Mingari, M.C.: HLA-E and HLA-E-bound peptides: recognition by subsets of NK and T cells. Curr. Pharm. Des. 2009, 15:3336–3344.

  • ■ Rodgers, J.R. and Cook, R.G.: MHC class Ib molecules bridge innate and acquired immunity. Nat. Rev. Immunol. 2005, 5:459–471.

1.2.18 Abschnitt 6.3.3

  • ■ Gendzekhadze, K., Norman, P.J., Abi-Rached, L., Graef, T., Moesta, A.K., Layrisse, Z., and Parham, P.: Co-evolution of KIR2DL3 with HLA-C in a human population retaining minimal essential diversity of KIR and HLA class I ligands. Proc. Natl Acad. Sci. USA 2009, 106:18692–18697.

  • ■ Godfrey, D.I., Stankovic, S., and Baxter, A.G.: Raising the NKT cell family. Nat. Immunol. 2010, 11:197–206.

  • ■ Hava, D.L., Brigl, M., van den Elzen, P., Zajonc, D.M., Wilson, I. A., and Brenner, M.B.: CD1 assembly and the formation of CD1-antigen complexes. Curr. Opin. Immunol. 2005, 17:88–94.

  • ■ Moody, D.B. and Besra, G.S.: Glycolipid targets of CD1-mediated T-cell responses. Immunology 2001, 104:243–251.

  • ■ Moody, D.B. and Porcelli, S.A.: CD1 trafficking: invariant chain gives a new twist to the tale. Immunity 2001, 15:861–865.

  • ■ Moody, D.B. and Porcelli, S.A.: Intracellular pathways of CD1 antigen presentation. Nat. Rev. Immunol. 2003, 3:11–22.

  • ■ Scharf, L., Li, N.S., Hawk, A.J., Garzón, D., Zhang, T., Fox, L.M., Kazen, A.R., Shah, S., Haddadian, E.J., Gumperz, J.E., et al.: The 2.5 Å structure of CD1c in complex with a mycobacterial lipid reveals an open groove ideally suited for diverse antigen presentation. Immunity 2010, 33:853–862.

  • ■ Schiefner, A., Fujio, M., Wu, D., Wong, C.H., and Wilson, I. A.: Structural evaluation of potent NKT cell agonists: implications for design of novel stimulatory ligands. J. Mol. Biol. 2009, 394:71–82.

1.2.19 Abschnitt 6.3.4

  • ■ Birkinshaw, R.W., Kjer-Nielsen, L., Eckle, S.B., McCluskey, J., and Rossjohn, J.: MAITs, MR1 and vitamin B metabolites. Curr. Opin. Immunol. 2014, 26:7–13.

  • ■ Kjer-Nielsen, L., Patel, O., Corbett, A.J., Le Nours, J., Meehan, B., Liu, L., Bhati, M., Chen, Z., Kostenko, L., Reantragoon, R., et al.: MR1 presents microbial vitamin B metabolites to MAIT cells. Nature 2012, 491:717–723.

  • ■ López-Sagaseta, J., Dulberger, C.L., Crooks, J.E., Parks, C.D., Luoma, A.M., McFedries, A., Van Rhijn, I., Saghatelian, A., and Adams, E.J.: The molecular basis for Mucosal-Associated Invariant T cell recognition of MR1 proteins. Proc. Natl Acad. Sci. USA 2013, 110:E1771–1778.

1.2.20 Abschnitt 6.3.5

  • ■ Chien, Y.H., Meyer, C., and Bonneville, M.: γδ T cells: first line of defense and beyond. Annu. Rev. Immunol. 2014, 32:121–155.

  • ■ Turchinovich, G. and Hayday, A.C.: Skint-1 identifies a common molecular mechanism for the development of interferon-γ-secreting versus interleukin-17-secreting γδ T cells. Immunity 2011, 35:59–68.

  • ■ Uldrich, A.P., Le Nours, J., Pellicci, D.G., Gherardin, N.A., McPherson, K.G., Lim, R.T., Patel, O., Beddoe, T., Gras, S., Rossjohn, J., et al.: CD1d-lipid antigen recognition by the γδ TCR. Nat. Immunol. 2013, 14:1137–1145.

  • ■ Willcox, C.R., Pitard, V., Netzer, S., Couzi, L., Salim, M., Silberzahn, T., Moreau, J.F., Hayday, A.C., Willcox, B.E., and Déchanet-Merville, J.: Cytomegalovirus and tumor stress surveillance by binding of a human γδ T cell antigen receptor to endothelial protein C receptor. Nat. Immunol. 2012, 13:872–879.

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer-Verlag GmbH Deutschland, ein Teil von Springer Nature

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Murphy, K., Weaver, C. (2018). Wie Antigene den T-Lymphocyten präsentiert werden. In: Janeway Immunologie. Springer Spektrum, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-56004-4_6

Download citation

Publish with us

Policies and ethics