Antigenerkennung durch B-Zell- und T-Zell-Rezeptoren

Appendices

Aufgaben

1 4.1 Richtig oder falsch

Aus einem Antikörper, der von Papain proteolytisch gespalten wird, geht ein Fragment hervor, das eine höhere Avidität für das zugehörige Antigen besitzt als der Antikörper, der von Pepsin gespalten wird.

1 4.2 Kurze Antwort

Warum ist die Bindung der CD4- und CD8-Corezeptoren wichtig für die Signalgebung der T-Zell-Rezeptoren?

1 4.3 Kurze Antwort

Warum und auf welche Weise ist es vorteilhaft, wenn der MHC-Locus heterozygot ist?

1 4.4 Bitte zuordnen

Welcher Begriff passt am besten zu welcher Beschreibung?

A.	Antigendeterminante	i.	die Struktur (das Epitop), die ein Antikörper erkennt
B.	Konformationsepitope, diskontinuierliche Epitope	ii.	Bereiche der V-Region, die eine signifikante Sequenzvariabilität aufweisen
C.	Lineare Epitope, kontinuierliche Epitope	iii.	ein Epitop, das aus einem einzigen Abschnitt einer Polypeptidkette besteht
D.	hypervariable Region	iv.	ein Epitop, das sich aus Aminosäuren von verschiedenen Teilen einer Polypeptidkette zusammensetzt, die durch die Proteinfaltung zusammengebracht werden

1 4.5 Bitte ergänzen

Die meisten Vertebraten, so auch der Mensch und die Maus, produzieren Antikörper, die aus ________ und ________ Ketten bestehen. Diese enthalten ________ Regionen, die Antigene erkennen, und ________ Regionen, welche die Klasse und den Isotyp der Antikörper festlegen. Camelidae und Knorpelfische produzieren jedoch ________ beziehungsweise ________, welche die Grundlage für die Herstellung von Einzelkettenantikörpern für klinische Anwendungen bilden.

1 4.6 Multiple Choice

Welche der folgenden Aussagen trifft nicht zu?

• A. Die α- und die β-Kette der T-Zell-Rezeptoren lagern sich zusammen, aber die α-Kette kann durch eine γ- oder eine δ-Kette ersetzt werden.

• B. Zwischen geladenen Aminosäuren kommt es zu elektrostatischen Wechselwirkungen (beispielsweise in Form einer Ionenbindung).

• C. Zwischen zwei hydrophoben Oberflächen kommt es zu hydrophoben Wechselwirkungen, wodurch Wasser ausgeschlossen wird.

• D. Antikörper enthalten in ihrer Antigenbindungsstelle häufig mehrere aromatische Aminosäuren wie Tyrosin.

• E. Die MHC-Restriktion ist ein Effekt, durch den T-Zellen eine spezifische Gruppe von Peptiden erkennen, die an ein bestimmtes MHC-Molekül gebunden ist.

1 4.7 Multiple Choice

Welches der folgenden Immunglobuline kommt bei ausgewachsenen gesunden Menschen oder Mäusen am häufigsten vor?

• A. IgA

• B. IgD

• C. IgE

• D. IgG

• E. IgM

1 4.8 Multiple Choice

Welche der folgenden Aussagen beschreibt die Struktur einer Immunglobulinfaltung?

• A. zwei antiparallele β-Faltblätter mit einem α-helikalen Verbindungsstück und einer Disulfidbrücke als Verknüpfung

• B. zwei β-Stränge, die durch eine Disulfidbrücke verbunden sind

• C. vier α-Helices, die durch zwei Disulfidbrücken verbunden sind

• D. sieben antiparallele α-Helices nacheinander

• E. ein β-Sandwich aus zwei β-Faltblättern, die zusammengefaltet und durch eine Disulfidbrücke verbunden sind

1 4.9 Multiple Choice

Antikörper sind an verschiedenen Stellen im Molekül beweglich, besonders in der Gelenkregion zwischen der Fc- und der Fab-Region sowie zu einem gewissen Maß an der Verbindungsstelle zwischen der V- und der C-Region. Welche der folgenden Eigenschaften eines Antikörpers werden durch diese Flexibilität nicht beeinflusst?

• A. Bindung kleiner Antigene (Haptene)

• B. Avidität gegenüber einem Antigen

• C. Affinität gegenüber einem Antigen

• D. Wechselwirkung mit antikörperbindenden Proteinen

• E. Bindung von räumlich getrennten Antigenen

1 4.10 Multiple Choice

Welche Region des Antigenrezeptors der B- und der T-Zellen besitzt für die Antigenerkennung und die Antigenspezifität die größte Bedeutung?

• A. FR1

• B. CDR1

• C. FR2

• D. CDR2

• E. FR3

• F. CDR3

• G. FR4

Literatur

1.1 Allgemeine Literatur

• ■ 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.

• ■ Garcia, K.C., Teyton, L., and Wilson, I. A.: Structural basis of T cell recognition. Annu. Rev. Immunol. 1999, 17:369–397.

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

• ■ Poljak, R.J.: Structure of antibodies and their complexes with antigens. Mol. Immunol. 1991, 28:1341–1345.

• ■ Rudolph, M.G., Stanfield, R.L., and Wilson, I.A: How TCRs bind MHCs, peptides, and coreceptors. Annu. Rev. Immunol. 2006, 24:419–466.

• ■ Sundberg, E.J. and Mariuzza, R.A.: Luxury accommodations: the expanding role of structural plasticity in protein-protein interactions. Structure 2000, 8:R137–R142.

1.2 Literatur zu den einzelnen Abschnitten

1.2.1 Abschnitt 4.1.1

• ■ Edelman, G.M.: Antibody structure and molecular immunology. Scand. J. Immunol. 1991, 34:4–22.

• ■ Faber, C., Shan, L., Fan, Z., Guddat, L.W., Furebring, C., Ohlin, M., Borrebaeck, C.A.K., and Edmundson, A.B.: Three-dimensional structure of a human Fab with high affinity for tetanus toxoid. Immunotechnology 1998, 3:253–270.

• ■ Harris, L.J., Larson, S.B., Hasel, K.W., Day, J., Greenwood, A., and McPherson, A.: The three-dimensional structure of an intact monoclonal antibody for canine lymphoma. Nature 1992, 360:369–372.

1.2.2 Abschnitte 4.1.2 und 4.1.3

• ■ Barclay, A.N., Brown, M.H., Law, S.K., McKnight, A.J., Tomlinson, M.G., and van der Merwe, P.A. (eds): The Leukocyte Antigen Factsbook, 2nd ed. London: Academic Press, 1997.

• ■ Brummendorf, T. and Lemmon, V.: Immunoglobulin superfamily receptors: cis-interactions, intracellular adapters and alternative splicing regulate adhesion. Curr. Opin. Cell Biol. 2001, 13:611–618.

• ■ Marchalonis, J.J. Jensen, I., and Schluter, S.F.: Structural, antigenic and evolutionary analyses of immunoglobulins and T cell receptors. J. Mol. Recog. 2002, 15:260–271.

• ■ Ramsland, P.A. and Farrugia, W.: Crystal structures of human antibodies: a detailed and unfinished tapestry of immunoglobulin gene products. J. Mol. Recog. 2002, 15:248–259.

1.2.3 Abschnitt 4.1.4

• ■ Porter, R.R.: Structural studies of immunoglobulins. Scand. J. Immunol. 1991, 34:382–389.

• ■ Yamaguchi, Y., Kim, H., Kato, K., Masuda, K., Shimada, I., and Arata, Y.: Proteolytic fragmentation with high specificity of mouse IgG—mapping of proteolytic cleavage sites in the hinge region. J. Immunol. Methods. 1995, 181:259–267.

1.2.4 Abschnitt 4.1.5

• ■ Gerstein, M., Lesk, A.M., and Chothia, C.: Structural mechanisms for domain movements in proteins. Biochemistry 1994, 33:6739–6749.

• ■ Jimenez, R., Salazar, G., Baldridge, K.K., and Romesberg, F.E.: Flexibility and molecular recognition in the immune system. Proc. Natl Acad. Sci. USA 2003, 100:92–97.

• ■ Saphire, E.O., Stanfield, R.L., Crispin, M.D., Parren, P.W., Rudd, P.M., Dwek, R.A., Burton, D.R., and Wilson, I. A.: Contrasting IgG structures reveal extreme asymmetry and flexibility. J. Mol. Biol. 2002, 319:9–18.

1.2.5 Abschnitt 4.2.1

• ■ Chitarra, V., Alzari, P.M., Bentley, G.A., Bhat, T.N., Eiselé, J.-L., Houdusse, A., Lescar, J., Souchon, H. and Poljak, R.J.: Three-dimensional structure of a heteroclitic antigen-antibody cross-reaction complex. Proc. Natl Acad. Sci. USA 1993, 90:7711–7715.

• ■ Decanniere, K., Muyldermans, S., and Wyns, L.: Canonical antigen-binding loop structures in immunoglobulins: more structures, more canonical classes? J. Mol. Biol. 2000, 300:83–91.

• ■ Gilliland, L.K., Norris, N.A., Marquardt, H., Tsu, T.T., Hayden, M.S., Neubauer, M.G., Yelton, D.E., Mittler, R.S., and Ledbetter, J.A.: Rapid and reliable cloning of antibody variable regions and generation of recombinant single-chain antibody fragments. Tissue Antigens 1996, 47:1–20.

• ■ Johnson, G. and Wu, T.T.: Kabat Database and its applications: 30 years after the first variability plot. Nucleic Acids Res. 2000, 28:214–218.

• ■ Wu, T.T. and Kabat, E.A.: An analysis of the sequences of the variable regions of Bence Jones proteins and myeloma light chains and their implications for antibody complementarity. J. Exp. Med. 1970, 132:211–250.

• ■ Xu, J., Deng, Q., Chen, J., Houk, K.N., Bartek, J., Hilvert, D., and Wilson, I. A.: Evolution of shape complementarity and catalytic efficiency from a primordial antibody template. Science 1999, 286:2345–2348.

1.2.6 Abschnitte 4.2.2 und 4.2.3

• ■ Ban, N., Day, J., Wang, X., Ferrone, S., and McPherson, A.: Crystal structure of an anti-anti-idiotype shows it to be self-complementary. J. Mol. Biol. 1996, 255:617–627.

• ■ Davies, D.R. and Cohen, G.H.: Interactions of protein antigens with antibodies. Proc. Natl Acad. Sci. USA 1996, 93:7–12.

• ■ Decanniere, K., Desmyter, A., Lauwereys, M., Ghahroudi, M.A., Muyldermans, S., and Wyns, L.: A single-domain antibody fragment in complex with RNase A: non-canonical loop structures and nanomolar affinity using two CDR loops. Structure Fold. Des. 1999, 7:361–370.

• ■ Padlan, E.A.: Anatomy of the antibody molecule. Mol. Immunol. 1994, 31:169–217.

• ■ Saphire, E.O., Parren, P.W., Pantophlet, R., Zwick, M.B., Morris, G.M., Rudd, P.M., Dwek, R.A., Stanfield, R.L., Burton, D.R., and Wilson, I. A.: Crystal structure of a neutralizing human IgG against HIV-1: a template for vaccine design. Science 2001, 293:1155–1159.

• ■ Stanfield, R.L. and Wilson, I. A.: Protein–peptide interactions. Curr. Opin. Struct. Biol. 1995, 5:103–113.

• ■ Tanner, J.J., Komissarov, A.A., and Deutscher, S.L.: Crystal structure of an antigen-binding fragment bound to single-stranded DNA. J. Mol. Biol. 2001, 314:807–822.

• ■ Wilson, I. A. and Stanfield, R.L.: Antibody–antigen interactions: new structures and new conformational changes. Curr. Opin. Struct. Biol. 1994, 4:857–867.

1.2.7 Abschnitt 4.2.4

• ■ Braden, B.C. Goldman, E.R., Mariuzza, R.A., and Poljak, R.J.: Anatomy of an antibody molecule: structure, kinetics, thermodynamics and mutational studies of the antilysozyme antibody D1.3. Immunol. Rev. 1998, 163:45–57.

• ■ Braden, B.C., and Poljak, R.J.: Structural features of the reactions between antibodies and protein antigens. FASEB J. 1995, 9:9–16.

• ■ Diamond, M.S., Pierson, T.C., and Fremont, D.H.: The structural immunology of antibody protection against West Nile virus. Immunol Rev. 2008, 225:212–225.

• ■ Lok, S.M., Kostyuchenko, V., Nybakken, G.E., Holdaway, H.A., Battisti, A.J., Sukupolvi-Petty, S., Sedlak, D., Fremont, D.H., Chipman, P.R., Roehrig, J.T., et al.: Binding of a neutralizing antibody to dengue virus alters the arrangement of surface glycoproteins. Nat. Struct. Mol. Biol. 2008, 15:312–317.

• ■ Ros, R., Schwesinger, F., Anselmetti, D., Kubon, M., Schäfer, R., Plückthun, A., and Tiefenauer, L.: Antigen binding forces of individually addressed single-chain Fv antibody molecules. Proc. Natl Acad. Sci. USA 1998, 95:7402–7405.

1.2.8 Abschnitt 4.2.5

• ■ Hamers-Casterman, C., Atarhouch, T., Muyldermans, S., Robinson, G., Hamers, C., Songa, E.B., Bendahman, N., and Hamers, R.: Naturally occurring antibodies devoid of light chains. Nature 1993, 363:446–448.

• ■ Muyldermans, S.: Nanobodies: natural single-domain antibodies. Annu. Rev. Biochem. 2013, 82:775–797.

• ■ Nguyen, V.K., Desmyter, A., and Muyldermans, S.: Functional heavy-chain antibodies in Camelidae. Adv. Immunol. 2001, 79:261–296.

1.2.9 Abschnitt 4.3.1

• ■ Al-Lazikani, B., Lesk, A.M., and Chothia, C.: Canonical structures for the hypervariable regions of T cell αβ receptors. J. Mol. Biol. 2000, 295:979–995.

• ■ Kjer-Nielsen, L., Clements, C.S., Brooks, A.G., Purcell, A.W., McCluskey, J., and Rossjohn, J.: The 1.5 Å crystal structure of a highly selected antiviral T cell receptor provides evidence for a structural basis of immunodominance. Structure (Camb.) 2002, 10:1521–1532.

• ■ Machius, M., Cianga, P., Deisenhofer, J., and Ward, E.S.: Crystal structure of a T cell receptor Vα11 (AV11S5) domain: new canonical forms for the first and second complementarity determining regions. J. Mol. Biol. 2001, 310:689–698.

1.2.10 Abschnitt 4.3.2

• ■ Garcia, K.C. and Adams, E.J.: How the T cell receptor sees antigen—a structural view. Cell 2005, 122:333–336.

• ■ Hennecke, J. and Wiley, D.C.: Structure of a complex of the human αβ T cell receptor (TCR) HA1.7, influenza hemagglutinin peptide, and major histocompatibility 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.

• ■ Luz, J.G., Huang, M., Garcia, K.C., Rudolph, M.G., Apostolopoulos, V., Teyton, L., and Wilson, I. A.: Structural comparison of allogeneic and syngeneic T cell receptor–peptide–major histocompatibility complex complexes: a buried alloreactive mutation subtly alters peptide presentation substantially increasing Vβ interactions. J. Exp. Med. 2002, 195:1175–1186.

• ■ Reinherz, E.L., Tan, K., Tang, L., Kern, P., Liu, J., Xiong, Y., Hussey, R.E., Smolyar, A., Hare, B., Zhang, R., et al.: The crystal structure of a T cell receptor in complex with peptide and MHC class II. Science 1999, 286:1913–1921.

• ■ Rudolph, M.G., Stanfield, R.L., and Wilson, I. A.: How TCRs bind MHCs, peptides, and coreceptors. Annu. Rev. Immunol. 2006, 24:419–466.

1.2.11 Abschnitte 4.3.3 und 4.3.4

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

• ■ Dessen, A., Lawrence, C.M., Cupo, S., Zaller, D.M., and Wiley, D.C.: X-ray crystal structure of HLA-DR4 (DRA*0101, DRB1*0401) complexed with a peptide from human collagen II. Immunity 1997, 7:473–481.

• ■ Fremont, D.H., Hendrickson, W.A., Marrack, P., and Kappler, J.: Structures of an MHC class II molecule with covalently bound single peptides. Science 1996, 272:1001–1004.

• ■ Fremont, D.H., Matsumura, M., Stura, E.A., Peterson, P.A., and Wilson, I. A.: Crystal structures of two viral peptides in complex with murine MHC class 1 H-2Kb. Science 1992, 257:919–927.

• ■ Fremont, D.H., Monnaie, D., Nelson, C.A., Hendrickson, W.A., and Unanue, E.R.: Crystal structure of I-Ak in complex with a dominant epitope of lysozyme. Immunity 1998, 8:305–317.

• ■ Macdonald, W.A., Purcell, A.W., Mifsud, N.A., Ely, L.K., Williams, D.S., Chang, L., Gorman, J.J., Clements, C.S., Kjer-Nielsen, L., Koelle, D.M., et al.: A naturally selected dimorphism within the HLA-B44 supertype alters class I structure, peptide repertoire, and T cell recognition. J. Exp. Med. 2003, 198:679–691.

• ■ Zhu, Y., Rudensky, A.Y., Corper, A.L., Teyton, L., and Wilson, I. A.: Crystal structure of MHC class II I-Ab in complex with a human CLIP peptide: prediction of an I-Ab peptide-binding motif. J. Mol. Biol. 2003, 326:1157–1174.

1.2.12 Abschnitt 4.3.5

• ■ Bouvier, M. and Wiley, D.C.: Importance of peptide amino and carboxyl termini to the stability of MHC class I molecules. Science 1994, 265:398–402.

• ■ Govindarajan, K.R., Kangueane, P., Tan, T.W., and Ranganathan, S.: MPID: MHC-Peptide Interaction Database for sequence–structure–function information on peptides binding to MHC molecules. Bioinformatics 2003, 19:309–310.

• ■ Saveanu, L., Fruci, D., and van Endert, P.: Beyond the proteasome: trimming, degradation and generation of MHC class I ligands by auxiliary proteases. Mol. Immunol. 2002, 39:203–215.

• ■ Weiss, G.A., Collins, E.J., Garboczi, D.N., Wiley, D.C., and Schreiber, S.L.: A tricyclic ring system replaces the variable regions of peptides presented by three alleles of human MHC class I molecules. Chem. Biol. 1995, 2:401–407.

1.2.13 Abschnitt 4.3.6

• ■ Conant, S.B. and Swanborg, R.H.: MHC class II peptide flanking residues of exogenous antigens influence recognition by autoreactive T cells. Autoimmun. Rev. 2003, 2:8–12.

• ■ Guan, P., Doytchinova, I. A., Zygouri, C., and Flower, D.R.: MHCPred: a server for quantitative prediction of peptide–MHC binding. Nucleic Acids Res. 2003, 31:3621–3624.

• ■ Lippolis, J.D., White, F.M., Marto, J.A., Luckey, C.J., Bullock, T.N., Shabanowitz, J., Hunt, D.F., and Engelhard, V. H.: Analysis of MHC class II antigen processing by quantitation of peptides that constitute nested sets. J. Immunol. 2002, 169:5089–5097.

• ■ Park, J.H., Lee, Y.J., Kim, K.L., and Cho, E.W.: Selective isolation and identification of HLA-DR-associated naturally processed and presented epitope peptides. Immunol. Invest. 2003, 32:155–169.

• ■ Rammensee, H.G.: Chemistry of peptides associated with MHC class I and class II molecules. Curr. Opin. Immunol. 1995, 7:85–96.

• ■ Rudensky, A.Y., Preston-Hurlburt, P., Hong, S.C., Barlow, A., and Janeway Jr., C.A.: Sequence analysis of peptides bound to MHC class II molecules. Nature 1991, 353:622–627.

• ■ Sercarz, E.E. and Maverakis, E.: MHC-guided processing: binding of large antigen fragments. Nat. Rev. Immunol. 2003, 3:621–629.

• ■ Sinnathamby, G. and Eisenlohr, L.C.: Presentation by recycling MHC class II molecules of an influenza hemagglutinin-derived epitope that is revealed in the early endosome by acidification. J. Immunol. 2003, 170:3504–3513.

1.2.14 Abschnitt 4.3.7

• ■ Buslepp, J., Wang, H., Biddison, W.E., Appella, E., and Collins, E.J.: A correlation between TCR Vα docking on MHC and CD8 dependence: implications for T cell selection. Immunity 2003, 19:595–606.

• ■ Ding, Y.H., Smith, K.J., Garboczi, D.N., Utz, U., Biddison, W.E., and Wiley, D.C.: Two human T cell receptors bind in a similar diagonal mode to the HLA-A2/Tax peptide complex using different TCR amino acids. Immunity 1998, 8:403–411.

• ■ Garcia, K.C., Degano, M., Pease, L.R., Huang, M., Peterson, P.A., Leyton, L., and Wilson, I. A.: Structural basis of plasticity in T cell receptor recognition of a self peptide-MHC antigen. Science 1998, 279:1166–1172.

• ■ Kjer-Nielsen, L., Clements, C.S., Purcell, A.W., Brooks, A.G., Whisstock, J.C., Burrows, S.R., McCluskey, J., and Rossjohn, J.: A structural basis for the selection of dominant αβ T cell receptors in antiviral immunity. Immunity 2003, 18:53–64.

• ■ Newell, E.W., Ely, L.K., Kruse, A.C., Reay, P.A., Rodriguez, S.N., Lin, A.E., Kuhns, M.S., Garcia, K.C., and Davis, M.M.: Structural basis of specificity and cross-reactivity in T cell receptors specific for cytochrome c-I-E(k). J. Immunol. 2011, 186:5823–5832.

• ■ Reiser, J.B., Darnault, C., Gregoire, C., Mosser, T., Mazza, G., Kearney, A., van der Merwe, P.A., Fontecilla-Camps, J.C., Housset, D., and Malissen, B.: CDR3 loop flexibility contributes to the degeneracy of TCR recognition. Nat. Immunol. 2003, 4:241–247.

• ■ Sant’Angelo, D.B., Waterbury, G., Preston-Hurlburt, P., Yoon, S.T., Medzhitov, R., Hong, S.C., and Janeway Jr., C.A.: The specificity and orientation of a TCR to its peptide-MHC class II ligands. Immunity 1996, 4:367–376.

• ■ Teng, M.K., Smolyar, A., Tse, A.G.D., Liu, J.H., Liu, J., Hussey, R.E., Nathenson, S.G., Chang, H.C., Reinherz, E.L., and Wang, J.H.: Identification of a common docking topology with substantial variation among different TCR–MHC–peptide complexes. Curr. Biol. 1998, 8:409–412.

1.2.15 Abschnitt 4.3.8

• ■ Chang, H.C., Tan, K., Ouyang, J., Parisini, E., Liu, J.H., Le, Y., Wang, X., Reinherz, E.L., and Wang, J.H.: Structural and mutational analyses of CD8αβ heterodimer and comparison with the CD8αα homodimer. Immunity 2005, 6:661–671.

• ■ Cheroutre, H., and Lambolez, F.: Doubting the TCR coreceptor function of CD8αα. Immunity 2008, 28:149–159.

• ■ Gao, G.F., Tormo, J., Gerth, U.C., Wyer, J.R., McMichael, A.J., Stuart, D.I., Bell, J.I., Jones, E.Y., and Jakobsen, B.Y.: Crystal structure of the complex between human CD8αα and HLA-A2. Nature 1997, 387:630–634.

• ■ Gaspar Jr., R. Bagossi, P., Bene, L., Matko, J., Szollosi, J., Tozser, J., Fesus, L., Waldmann, T.A., and Damjanovich, S.: Clustering of class I HLA oligomers with CD8 and TCR: three-dimensional models based on fluorescence resonance energy transfer and crystallographic data. J. Immunol. 2001, 166:5078–5086.

• ■ Kim, P.W., Sun, Z.Y., Blacklow, S.C., Wagner, G., and Eck, M.J.: A zinc clasp structure tethers Lck to T cell coreceptors CD4 and CD8. Science 2003, 301:1725–1728.

• ■ Moody, A.M., North, S.J., Reinhold, B., Van Dyken, S.J., Rogers, M. E., Panico, M., Dell, A., Morris, H.R., Marth, J.D., and Reinherz, E.L.: Sialic acid capping of CD8β core 1-O-glycans controls thymocyte-major histocompatibility complex class I interaction. J. Biol. Chem. 2003, 278:7240–7260.

• ■ Walker, L.J., Marrinan, E., Muenchhoff, M., Ferguson, J., Kloverpris, H., Cheroutre, H., Barnes, E., Goulder, P., and Klenerman, P.: CD8αα expression marks terminally differentiated human CD8+ T cells expanded in chronic viral infection. Front Immunol. 2013, 4:223.

• ■ 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.

• ■ Wang, R., Natarajan, K., and Margulies, D.H.: Structural basis of the CD8αβ/MHC class I interaction: focused recognition orients CD8β to a T cell proximal position. J. Immunol. 2009, 183:2554–2564.

• ■ Wang, X.X., Li, Y., Yin, Y., Mo, M., Wang, Q., Gao, W., Wang, L., and Mariuzza, R.A.: Affinity maturation of human CD4 by yeast surface display and crystal structure of a CD4-HLA-DR1 complex. Proc. Natl Acad. Sci. USA 2011, 108:15960–15965.

• ■ Wu, H., Kwong, P.D., and Hendrickson, W.A.: Dimeric association and segmental variability in the structure of human CD4. Nature 1997, 387:527–530.

• ■ Yin, Y., Wang, X.X., and Mariuzza, R.A.: Crystal structure of a complete ternary complex of T-cell receptor, peptide-MHC, and CD4. Proc. Natl Acad. Sci. USA 2012, 109:5405–5410.

• ■ Zamoyska, R.: CD4 and CD8: modulators of T cell receptor recognition of antigen and of immune responses? Curr. Opin. Immunol. 1998, 10:82–86.

1.2.16 Abschnitt 4.3.9

• ■ Steimle, V., Siegrist, C.A., Mottet, A., Lisowska-Grospierre, B., and Mach, B.: Regulation of MHC class II expression by interferon-γ mediated by the transactivator gene CIITA. Science 1994, 265:106–109.

1.2.17 Abschnitt 4.3.10

• ■ Adams, E.J., Chien, Y.H., and Garcia, K.C.: Structure of a γδ T cell receptor in complex with the nonclassical MHC T22. Science 2005, 308:227–231.

• ■ Allison, T.J. and Garboczi, D.N.: Structure of γδ T cell receptors and their recognition of non-peptide antigens. Mol. Immunol. 2002, 38:1051–1061.

• ■ Allison, T.J., Winter, C.C., Fournie, J.J., Bonneville, M., and Garboczi, D.N.: Structure of a human γδ T-cell antigen receptor. Nature 2001, 411:820–824.

• ■ Das, H., Wang, L., Kamath, A., and Bukowski, J.F.: Vγ2Vδ2 T-cell receptor-mediated recognition of aminobisphosphonates. Blood 2001, 98:1616–1618.

• ■ Luoma, A.M., Castro, C.D., Mayassi, T., Bembinster, L.A., Bai, L., Picard, D., Anderson, B., Scharf, L., Kung, J.E., Sibener, L.V., et al.: Crystal structure of Vδ1 T cell receptor in complex with CD1d-sulfatide shows MHC-like recognition of a self-lipid by human γδ T cells. Immunity 2013, 39:1032–1042.

• ■ Vantourout, P. and Hayday, A.: Six-of-the-best: unique contributions of γδ T cells to immunology. Nat. Rev. Immunol. 2013, 13:88–100.

• ■ Wilson, I. A. and Stanfield, R.L.: Unraveling the mysteries of γδ T cell recognition. Nat. Immunol. 2001, 2:579–581.

• ■ Wingren, C., Crowley, M.P., Degano, M., Chien, Y., and Wilson, I. A.: Crystal structure of a γδ T cell receptor ligand T22: a truncated MHC-like fold. Science 2000, 287:310–314.

• ■ Wu, J., Groh, V., and Spies, T.: T cell antigen receptor engagement and specificity in the recognition of stress-inducible MHC class I-related chains by human epithelial γδ T cells. J. Immunol. 2002, 169:1236–1240.