Abstract
In our context the most important part is the peptide-binding groove. It is made up of the αl and α2 domains. Amino acids lα, to 48α1, and 94α2 to 135α2 form a β-pleated sheet which makes up the floor of the groove1,2 (see Fig. 3.1). The remaining parts of both domains are in α-helical conformation and form the rims of the groove. The peptide, usually but not always nine AA long, lies more or less extended between the two α-helical rims; both N and C termini are tightly fixed in the edges of the groove.3 Clusters of conserved residues form hydrogen bonds with either of the termini. For the peptide N-terminus, these are Tyr7, Tyr59, Tyr71, Trp167, and Tyr159; for the C-terminus, Tyr84, Thr143, Lys146 and Trp147 form these bonds.2 Most of the peptide-binding affinity is brought about by these forces, at least for those peptides of eight to ten AA, whose termini are then buried within the binding site.3 Some longer ligands, however, are loose at one end so that they protrude over the groove’s ends.4 Other long peptides have their termini fixed in the groove but have their middle part bulged out to accommodate the extra length.5 The specificity of interactions between peptide and the groove comes about by many contacts between peptide side chains and MHC residues. These contacts, apart from contributing to the binding forces, are responsible for the allele-specific binding characteristics of class I molecules.6,7 The most prominent contacts of this kind are produced by pockets within the binding cleft. Specificity and location of these pockets vary considerably between different MHC alleles; thus, MHC sequence polymorphism directly affects peptide binding specificity. For example, A*0201 binds peptides with a large aliphatic side chain (Leu, Ile, or Met) at position 2, and a smaller aliphatic side chain (Leu or Val) at the C-terminus, which is mostly P9.8
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References
Bjorkman PJ, Saper MA, Samraoui B et al. Structure of the human class I histo- 13. compatibility antigen, HLA-A2. Nature 1987; 329: 506–12.
Stern LJ, Wiley DC. Antigenic peptide binding by class I and class II histocompatibility proteins. Structure 1994; 2: 245–51.
Bouvier M, Wiley DC. Importance of peptide amino and carboxyl termini to the stability of MHC class I molecules. Science 1994; 265: 398–402.
Collins EJ, Garboczi DN, Wiley DC. Three-dimensional structure of a peptide extending from one end of a class I MHC binding site. Nature 1994; 371: 626–9.
Guo HC, Jardetzky TS, Garrett TP et al. Different length peptides bind to HLAAw68 similarly at their ends but bulge out in the middle. Nature 1992; 360: 364–6.
Guo HC, Madden DR, Silver ML et al. Comparison of the P2 specificity pocket in three human histocompatibility antigens: HLA-A*6801, HLA-A*0201, and HLA-B*2705. Proc Natl Acad Sci USA 1993; 90: 8053–7.
Garboczi DN, Madden DR, Wiley DC. Five viral peptide-HLA-A2 co-crystals. Simultaneous space group determination and X-ray data collection. J Mol Biol 1994; 239: 581–7.
Falk K, Rötzschke O, Stevanovie S et al. Allele-specific motifs revealed by sequencing of self-peptides eluted from 20. MHC molecules. Nature 1991; 351: 290–6.
Falk K, Rötzschke O, Takiguchi M et al. Peptide motifs of HLA-A1, -All, -A31, and -A33 molecules. Immunogenetics 1994; 40: 238–41.
DiBrino M, Tsuchida T, Turner RV et al. HLA-Al and HLA-A3 T cell epitopes derived from influenza virus proteins predicted from peptide binding motifs. J Immunol 1993; 151: 5930–5.
Silver ML, Guo HC, Strominger JL et al. Atomic structure of a human MHC molecule presenting an influenza virus peptide. Nature 1992; 360: 300–1.
Young AC, Zhang W, Sacchettini JC et al. The three-dimensional structure of H-2Db at 2.4 A resolution: implicationsfor antigen-determinant selection. Cell 1994; 76: 39–50.
Smith KJ, Reid SW, Harlos K et al. Bound water structure and polymorphic amino acids act together to allow the binding of different peptides to MHC class I HLA-B53. Immunity 1996; 4: 215–28.
Fremont DH, Matsumura M, Stura EA et al. Crystal structures of two viral pep- tides in complex with murine MHC class I H-2Kb. Science 1992; 257: 919–27.
Falk K, Rötzschke O. Consensus motifs and peptide ligands of MHC class I molecules. Semin Immunol 1993; 5: 81–94.
Matsumura M, Fremont DH, Peterson PA et al. Emerging principles for the recognition of peptide antigens by MHC class I molecules. Science 1992; 257: 927–34.
Chelvanayagam G. A roadmap for HLA-A, HLA-B and HLA-C allotype peptide binding specificities. Immunogenetics 1996; 45: 15–26.
Madden DR, Garboczi DN, Wiley DC. The antigenic identity of peptide-MHC complexes: a comparison of the conformations of five viral peptides presented by HLA-A2 [published erratum appears in Cell 1994; 76:410]. Cell 1993; 75: 693–708.
Jackson MR, Peterson PA. Assembly and intracellular transport of MHC class I molecules. Annu Rev Cell Biol 1993; 9: 207–35.
Wang CR, Castano AR, Peterson PA et al. Nonclassical binding of formylated peptide in crystal structure of the MHC class Ib molecule H2–M3. Cell 1995; 82: 655–64.
Smith KJ, Reid SW, Stuart DI et al. An altered position of the alpha 2 helix of MHC class I is revealed by the crystal structure of HLA-B*3501. Immunity 1996; 4: 203–13.
Nandi D, Jiang H, Monaco JJ. Identification of MECL-1 (LMP-l0) as the third IFN-gamma-inducible proteasome subunit. J Immunol 1996; 156: 2361–4.
Rammensee HG, Robinson PJ, Crisanti A et al. Restricted recognition of beta 2microglobulin by cytotoxic T lymphocytes. Nature 1986; 319: 502–4.
Sun J, Leahy DJ, Kavathas PB. Interaction between CD8 and major histocompatibility complex (MHC) class I mediated by multiple contact surfaces that include the alpha 2 and alpha 3 domains of MHC class I. J Exp Med 1995; 182: 1275–80.
Saper MA, Bjorkman PJ, Wiley DC. Refined structure of the human histocompatibility antigen HLA-A2 at 2.6 A resolution. J Mol Biol 1991; 219: 277–319.
Garboczi DN, Gosh P, Utz U et al. Structure of the complex between human T cell receptor, viral peptide and HLA-A2. Nature 1996; 384: 134–41.
Garcia KC, Degano M, Stanfield RL et al. An alpha-beta T cell receptor structure at 2.5 A and its orientation in the TCR-MHC complex. Science 1996; 274: 209–19.
Jardetzky TS, Brown JH, Gorga JC et al. Crystallographic analysis of endogenous peptides associated with HLA-DR1 suggests a common, polyproline II-like conformation for bound peptides. Proc Natl Acad Sci USA 1996; 93: 734–8.
Ghosh P, Amaya M, Mellins E et al. The structure of an intermediate in class II MHC maturation: CLIP bound to HLADR3. Nature 1995; 378: 457–62.
Stern LJ, Brown JH, Jardetzky TS et al. Crystal structure of the human class II MHC protein HLA-DR1 complexed with an influenza virus peptide. Nature 1994; 368: 215–21.
Brown JH, Jardetzky TS, Gorga JC et al. Three-dimensional structure of the human class II histocompatibility antigen HLA-DR1. Nature 1993; 364: 33–9.
Rammensee HG. Chemistry of peptides associated with MHC class I and class II molecules. Curr Opin Immunol 1995; 7: 85–96.
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Rammensee, HG., Bachmann, J., Stevanović, S. (1997). The Structure. In: MHC Ligands and Peptide Motifs. Molecular Biology Intelligence Unit. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-22162-4_3
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DOI: https://doi.org/10.1007/978-3-662-22162-4_3
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