Skip to main content
SpringerLink
Log in

MHC and MHC-Like Molecules: Structural Perspectives on the Design of Molecular Vaccines

  • Chapter
Multichain Immune Recognition Receptor Signaling

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 640))

Abstract

Major histocompatibility complex (MHC) molecules bind and present short antigenic peptide fragments on the surface of antigen presenting cells (APCs) to T-cell receptors. Recognition of peptide-MHC complexes by T-cells initiates a cascade of signals in T-cells and activated cells either destroy or help to destroy the APC. The MHCs are divided into three subgroups: MHC class I, MHC class II and MHC class III. In addition, nonclassical MHC molecules and MHC -like molecules play a pivotal role in shaping our understanding of the immune response. In the design of molecular vaccines for the treatment of diseases, an understanding of the three-dimensional structure of MHC, its interaction with peptide ligands and its interaction with the T-cell receptor are important prerequisites, all of which are discussed herein.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Kindred B, Shreffler DC. H-2 dependence of co-operation between T and B cells in vivo. J Immunol 1972; 109:940–3.

    PubMed  CAS  Google Scholar 

  2. Rosenthal AS, Shevach EM. Function of macrophages in antigen recognition by guinea pig T-lymphocytes. I. Requirement for histocompatible macrophages and lymphocytes. J Exp Med 1973; 138:1194–212.

    Article  PubMed  CAS  Google Scholar 

  3. Zinkernagel RM, Doherty PC. Restriction of in vitro T-cell-mediated cytotoxicity in lymphocytic choriomeningitis within a syngeneic or semiallogeneic system. Nature 1974; 248:701–2.

    Article  PubMed  CAS  Google Scholar 

  4. Harding CV, Song R. Phagocytic processing of exogenous particulate antigens by macrophages for presentation by class I MHC molecules. J Immunol 1994; 153:4925–33.

    PubMed  CAS  Google Scholar 

  5. Zwickey HL, Potter TA. Antigen secreted from noncytosoiic Listeria monocytogenes is processed by the classical MHC class I processing pathway. J Immunol 1999; 162:6341–50.

    PubMed  CAS  Google Scholar 

  6. Bjorkman PJ, Saper MA, Samraoui B et al. Structure of the human class I histocompatibility antigen, HLA-A2. Nature 1987; 329:506–12.

    Article  PubMed  CAS  Google Scholar 

  7. Apostoiopoulos V, Lazoura E. Noncanonical peptides in complex with MHC class I. Expert Rev Vaccines 2004; 3:151–62.

    Article  Google Scholar 

  8. Apostoiopoulos V, McKenzie IF, Wilson IA. Getting into the groove: Unusual features of peptide binding to MHC class I molecules and implications in vaccine design. Front Biosci 2001; 6:D1311–20.

    Article  Google Scholar 

  9. Apostoiopoulos V, Yu M, McKenzie IF et al. Structural implications for the design of molecular vaccines. Curr Opin Mol Ther 2000; 2:29–36.

    Google Scholar 

  10. Lazoura E, Apostolopoulos V. Insights into peptide-based vaccine design for cancer immunotherapy. Curr Med Chem 2005; 12:1481–94.

    Article  PubMed  CAS  Google Scholar 

  11. Lazoura E, Apostolopoulos V. Rational Peptide-based vaccine design for cancer immunotherapeutic applications. Curr Med Chem 2005; 12:629–39.

    Article  PubMed  CAS  Google Scholar 

  12. Pietersz GA, Pouniotis DS, Apostolopoulos V. Design of peptide-based vaccines for cancer. Curr Med Chem 2006; 13:1591–607.

    Article  PubMed  CAS  Google Scholar 

  13. Garrett TP, Saper MA, Bjorkman PJ et al. Specificity pockets for the side chains of peptide antigens in HLA-Aw68. Nature 1989; 342:692–6.

    Article  PubMed  CAS  Google Scholar 

  14. Rammensee HG, Friede T, Stevanoviic S. MHC Hgands and peptide motifs: First listing. Immunogenetics 1995; 41:178–228.

    Article  PubMed  CAS  Google Scholar 

  15. Falk K, Rotzschke O, Stevanovic S et al. Allele-specific motifs revealed by sequencing of self-peptides eluted from MHC molecules. Nature 1991; 351:290–6.

    Article  PubMed  CAS  Google Scholar 

  16. Rammensee HG. Chemistry of peptides associated with MHC class I and class II molecules. Curr Opin Immunol 1995; 7:85–96.

    Article  PubMed  CAS  Google Scholar 

  17. Haurum JS, Hoier IB, Arsequell G et al. Presentation of cytosolic glycosylated peptides by human class I major histocompatibility complex molecules in vivo. J Exp Med 1999; 190:145–50.

    Article  PubMed  CAS  Google Scholar 

  18. Glithero A, Tormo J, Haurum JS et al. Crystal structures of two H-2Db/glycopeptide complexes suggest a molecular basis for CTL cross-reactivity. Immunity 1999; 10:63–74.

    Article  PubMed  CAS  Google Scholar 

  19. Speir JA, Abdel-Motal UM, Jondal M et al. Crystal structure of an MHC class I presented glycopeptide that generates carbohydrate-specific CTL. Immunity 1999; 10:51–61.

    Article  PubMed  CAS  Google Scholar 

  20. Apostolopoulos V, Yuriev E, Ramsland PA et al. A glycopeptide in complex with MHC class I uses the GalNAc residue as an anchor. Proc Natl Acad Sci USA 2003; 100:15029–34.

    Article  PubMed  CAS  Google Scholar 

  21. Andersen MH, Bonfill JE, Neisig A et al. Phosphorylated peptides can be transported by TAP molecules, presented by class I MHC molecules and recognized by phosphopeptide-specific CTL. J Immunol 1999; 163:3812–8.

    PubMed  CAS  Google Scholar 

  22. Apostolopoulos V, Haurum JS, McKenzie IF. MUCl peptide epitopes associated with five different H-2 class I molecules. Eur J Immunol 1997; 27:2579–87.

    Article  PubMed  CAS  Google Scholar 

  23. Apostolopoulos V, Karanikas V, Haurum JS et al. Induction of HLA-A2-restricted CTLs to the mucin 1 human breast cancer antigen. J Immunol 1997; 159:5211–8.

    PubMed  CAS  Google Scholar 

  24. Reddehase MJ, Rothbard JB, Koszinowski UH. A pentapeptide as minimal antigenic determinant for MHC class I-restricted T-lymphocytes. Nature 1989; 337:651–3.

    Article  PubMed  CAS  Google Scholar 

  25. Horig H, Young AC, Papadopoulos NJ et al. Binding of longer peptides to the H-2Kb heterodimer is restricted to peptides extended at their C terminus: Refinement of the inherent MHC class I peptide binding criteria. J Immunol 1999; 163:4434–41.

    PubMed  CAS  Google Scholar 

  26. Rudolph MG, Stevens J, Speir JA et al. Crystal structures of two rat MHC class Ia (RTl-A) molecules that are associated differentially with peptide transporter alleles TAP-A and TAP-B. J Mol Biol 2002; 324:975–90.

    Article  PubMed  CAS  Google Scholar 

  27. Speir JA, Stevens J, Joly E et al. Two different, highly exposed, bulged structures for an unusually long peptide bound to rat MHC class I RTl-Aa. Immunity 2001; 14:81–92.

    Article  PubMed  CAS  Google Scholar 

  28. Tynan FE, Burrows SR, Buckle AM et al. T-cell receptor recognition of a’ super-bulged’ major histocompatibility complex class I-bound peptide. Nat Immunol 2005; 6:1114–22.

    Article  PubMed  CAS  Google Scholar 

  29. Miles JJ, Elhassen D, Borg NA et al. CTL recognition of a bulged viral peptide involves biased TCR selection. J Immunol 2005; 175:3826–34.

    PubMed  CAS  Google Scholar 

  30. Tynan FE, Borg NA, Miles JJ et al. High resolution structures of highly bulged viral epitopes bound to major histocompatibility complex class I. Implications for T-cell receptor engagement and T-cell immunodominance. J Biol Chem 2005; 280:23900–9.

    Article  PubMed  CAS  Google Scholar 

  31. Burrows SR, Rossjohn J, McCluskey J. Have we cut ourselves too short in mapping CTL epitopes? Trends Immunol 2006; 27:11–6.

    Article  PubMed  CAS  Google Scholar 

  32. Samino Y, Lopez D, Guil S et al. A long N-terminal-extended nested set of abundant and antigenic major histocompatibility complex class I natural ligands from HIV envelope protein. J Biol Chem 2006; 281:6358–65.

    Article  PubMed  CAS  Google Scholar 

  33. 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.

    Article  PubMed  CAS  Google Scholar 

  34. Chen Y, Sidney J, Southwood S et al. Naturally processed peptides longer than nine amino acid residues bind to the class I MHC molecule HLA-A2.1 with high affinity and in different conformations. J Immunol 1994; 152:2874–81.

    PubMed  CAS  Google Scholar 

  35. Apostolopoulos V, Yu M, Corper AL et al. Crystal structure of a noncanonical low-affinity peptide complexed with MHC class I: A new approach for vaccine design. J Mol Biol 2002; 318:1293–305.

    Article  PubMed  CAS  Google Scholar 

  36. Eisen HN, Sykulev Y, Tsomides TJ. Antigen-specific T-cell receptors and their reactions with complexes formed by peptides with major histocompatibility complex proteins. Adv Protein Chem 1996; 49:1–56.

    Article  PubMed  CAS  Google Scholar 

  37. Gillanders WE, Hanson HL, Rubocki RJ et al. Class I-restricted cytotoxic T-cell recognition of split peptide ligands. Int Immunol 1997; 9:81–9.

    Article  PubMed  CAS  Google Scholar 

  38. Glithero A, Tormo J, Doering K et al. The crystal structure of H-2D(b) complexed with a partial peptide epitope suggests a major histocompatibility complex class I assembly intermediate. J Biol Chem 2006; 281:12699–704.

    Article  PubMed  CAS  Google Scholar 

  39. Apostolopoulos V, Yu M, Corper AL et al. Crystal structure of a noncanonical high affinity peptide complexed with MHC class I: a novel use of alternative anchors. J Mol Biol 2002; 318:1307–16.

    Article  PubMed  CAS  Google Scholar 

  40. Apostolopoulos V, Chelvanayagam G, Xing PX et al. Anti-MUCl antibodies react directly with MUCl peptides presented by class I H2 and HLA molecules. J Immunol 1998; 161:767–75.

    PubMed  CAS  Google Scholar 

  41. Chelvanayagam G, Apostolopoulos V, McKenzie IF. Milestones in the molecular structure of the major histocompatibility complex. Protein Eng 1997; 10:471–4.

    Article  PubMed  CAS  Google Scholar 

  42. Meijers R, Lai CC, Yang Y et al. Crystal structures of murine MHC Class I H-2 D(b) and K(b) molecules in complex with CTL epitopes from influenza A virus: Implications for TCR repertoire selection and immunodominance. J Mol Biol 2005; 345:1099–110.

    Article  PubMed  CAS  Google Scholar 

  43. Pieters J. MHC class II restricted antigen presentation. Curr Opin Immunol 1997; 9:89–96.

    Article  PubMed  CAS  Google Scholar 

  44. Watts C. Capture and processing of exogenous antigens for presentation on MHC molecules. Annu Rev Immunol 1997; 15:821–50.

    Article  PubMed  CAS  Google Scholar 

  45. Kropshofer H, Hammerling GJ, Vogt AB. How HLA-DM edits the MHC class II peptide repertoire: Survival of the fittest? Immunol Today 1997; 18:77–82.

    Article  PubMed  CAS  Google Scholar 

  46. Brown JH, Jardetzky TS, Gorga JC et al. Three-dimensional structure of the human class II histocom-patibility antigen HLA-DRl. Nature 1993; 364:33–9.

    Article  PubMed  CAS  Google Scholar 

  47. Stern LJ, Brown JH, Jardetzky TS et al. Crystal structure of the human class II MHC protein HLA-DRl complexed with an influenza virus peptide. Nature 1994; 368:215–21.

    Article  PubMed  CAS  Google Scholar 

  48. Dessen A, Lawrence CM, Cupo S et al. X-ray crystal structure of HLA-DR4 (DRA*0101, DRB1*0401) complexed with a peptide from human collagen II. Immunity 1997; 7:473–81.

    Article  PubMed  CAS  Google Scholar 

  49. Ghosh P, Amaya M, Mellins E et al. The structure of an intermediate in class II MHC maturation: CLIP bound to HLA-DR3. Nature 1995; 378:457–62.

    Article  PubMed  CAS  Google Scholar 

  50. Fremont DH, Hendrickson WA, Marrack P et al. Structures of an MHC class II molecule with covalently bound single peptides. Science 1996; 272:1001–4.

    Article  PubMed  CAS  Google Scholar 

  51. Scott CA, Peterson PA, Teyton L et al. Crystal structures of two I-Ad-peptide complexes reveal that high affinity can be achieved without large anchor residues. Immunity 1998; 8:319–29.

    Article  PubMed  CAS  Google Scholar 

  52. Melvold RW, Wang K, Kohn HI. Histocompatibility gene mutation rates in the mouse: A 25-year review. Immunogenetics 1997; 47:44–54.

    Article  PubMed  CAS  Google Scholar 

  53. Luz JG, Huang M, Garcia KC et al. Structural comparison of allogeneic and syngeneic T-cell receptor-peptide-major histocompatibility complex complexes: A buried alloreactive mutation subtly alters peptide presentation substantially increasing V(beta) Interactions. J Exp Med 2002; 195:1175–86.

    Article  PubMed  CAS  Google Scholar 

  54. Rodgers JR, Cook RG. MHC class Ib molecules bridge innate and acquired immunity. Nat Rev Immunol 2005; 5:459–71.

    Article  PubMed  CAS  Google Scholar 

  55. Borrego F, Ulbrecht M, Weiss EH et al. Recognition of human histocompatibility leukocyte antigen (HLA)-E complexed with HLA class I signal sequence-derived peptides by CD94/NKG2 confers protection from natural killer cell-mediated lysis. J Exp Med 1998; 187:813–8.

    Article  PubMed  CAS  Google Scholar 

  56. Braud VM, Allan DS, O’Callaghan CA et al. HLA-E binds to natural killer cell receptors CD94/NKG2A, B and C. Nature 1998; 391:795–9.

    Article  PubMed  CAS  Google Scholar 

  57. Pietra G, Romagnani C, Mazzarino P et al. HLA-E-restricted recognition of cytomegalovirus-derived peptides by human CD8+ cytolytic T-lymphocytes. Proc Natl Acad Sci USA 2003; 100:10896–901.

    Article  PubMed  CAS  Google Scholar 

  58. Allan DS, Colonna M, Lanier LL et al. Tetrameric complexes of human histocompatibility leukocyte antigen (HLA)-G bind to peripheral blood myelomonocytic cells. J Exp Med 1999; 189:1149–56.

    Article  PubMed  CAS  Google Scholar 

  59. Mallet V, Blaschitz A, Crisa L et al. HLA-G in the human thymus: A subpopulation of medullary epithelial but not CD83(+) dendritic cells expresses HLA-G as a membrane-bound and soluble protein. Int Immunol 1999; 11:889–98.

    Article  PubMed  CAS  Google Scholar 

  60. Ishitani A, Sageshima N, Lee N et al. Protein expression and peptide binding suggest unique and interacting functional roles for HLA-E, F and G in maternal-placental immune recognition. J Immunol 2003; 171:1376–84.

    PubMed  CAS  Google Scholar 

  61. Chiang EY, Stroynowski I. A nonclassical MHC class I molecule restricts CTL-mediated rejection of a syngeneic melanoma tumor. J Immimol 2004; 173:4394–401.

    CAS  Google Scholar 

  62. Sullivan LC, Hoare HL, McCluskcy J et al. A structural perspective on MHC class Ib molecules in adaptive immunity. Trends Immunol 2006.

    Google Scholar 

  63. Clements CS, Kjer-Nielsen L, Kostenko L et al. Crystal structure of HLA-G: A nonclassical MHC class I molecule expressed at the fetal-maternal interface. Proc Natl Acad Sci USA 2005; 102:3360–5.

    Article  PubMed  CAS  Google Scholar 

  64. Joyce S, Tabaczewski P, Angeletti RH et al. A nonpolymorphic major histocompatibility complex class Ib molecule binds a large array of diverse self-peptides. J Exp Med 1994; 179:579–88.

    Article  PubMed  CAS  Google Scholar 

  65. He X, Tabaczewski P, Ho J et al. Promiscuous antigen presentation by the nonclassical MHC Ib Qa-2 is enabled by a shallow, hydrophobic groove and self-stabilized peptide conformation. Structure 2001; 9:1213–24.

    Article  PubMed  CAS  Google Scholar 

  66. 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.

    Article  PubMed  CAS  Google Scholar 

  67. Lebron JA, Bennett MJ, Vaughn DE et al. Crystal structure of the hemochromatosis protein HFE and characterization of its interaction with transferrin receptor. Cell 1998; 93:111–23.

    Article  PubMed  CAS  Google Scholar 

  68. Alfonso C, Karlsson L. Nonclassical MHC class II molecules. Annu Rev Immunol 2000; 18:113–42.

    Article  PubMed  CAS  Google Scholar 

  69. Garboczi DN, Ghosh P, Utz U et al. Structure of the complex between human T-cell receptor, viral peptide and HLA-A2. Nature 1996; 384:134–41.

    Article  PubMed  CAS  Google Scholar 

  70. Garcia KC, Degano M, Stanfield RL et al. An alphabeta T-cell receptor structure at 2.5 A and its orientation in the TCR-MHC complex. Science 1996; 274:209–19.

    Article  PubMed  CAS  Google Scholar 

  71. Garcia KC, Degano M, Pease LR et al. Structural basis of plasticity in T-cell receptor recognition of a self peptide-MHC antigen. Science 1998; 279:1166–72.

    Article  PubMed  CAS  Google Scholar 

  72. Reinherz EL, Tan K, Tang L et al. Ihe crystal structure of a T-cell receptor in complex with peptide and MHC class II. Science 1999; 286:1913–21.

    Article  PubMed  CAS  Google Scholar 

  73. Hoare HL, Sullivan LC, Pietra G et al. Structural basis for a major histocompatibility complex class Ib-restricted T-cell response. Nat Immunol 2006; 7:256–64.

    Article  PubMed  CAS  Google Scholar 

  74. Adams EJ, Chien YH, Garcia KC. Structure of a gammadelta T-cell receptor in complex with the nonclassical MHC T22. Science 2005; 308:227–31.

    Article  PubMed  CAS  Google Scholar 

  75. Burmeister WP, Huber AH, Bjorkman PJ. Crystal structure of the complex of rat neonatal Fc receptor with Fc. Nature 1994; 372:379–83.

    Article  PubMed  CAS  Google Scholar 

  76. Rudolph MG, Stanfield RL, Wilson IA. How TCRs bind MHCs, peptides and coreceptors. Annu Rev Immunol 2006; 24:419–66.

    Article  PubMed  CAS  Google Scholar 

  77. Chatterjee D, Khoo KH. Mycobacterial lipoarabinomannan: An extraordinary lipoheteroglycan with profound physiological effects. Glycobiology 1998; 8:113–20.

    Article  PubMed  CAS  Google Scholar 

  78. Zeng Z, Castano AR, Segelke BW et al. Crystal structure of mouse CDl: An MHC-like fold with a large hydrophobic binding groove. Science 1997; 277:339–45.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Burnet Institute at Austin, Kronheimer Building, Studley Road, Heidelberg, VIC 3084, Australia

    Vasso Apostolopoulos, Eliada Lazoura & Minmin Yu

Authors
  1. Vasso Apostolopoulos
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Eliada Lazoura
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Minmin Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Pathology, University of Massachusetts Medical School, Worcester, Massachusetts, USA

    Alexander B. Sigalov PhD

Rights and permissions

Reprints and permissions

Copyright information

© 2008 Landes Bioscience and Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Apostolopoulos, V., Lazoura, E., Yu, M. (2008). MHC and MHC-Like Molecules: Structural Perspectives on the Design of Molecular Vaccines. In: Sigalov, A.B. (eds) Multichain Immune Recognition Receptor Signaling. Advances in Experimental Medicine and Biology, vol 640. Springer, New York, NY. https://doi.org/10.1007/978-0-387-09789-3_19

Download citation

Publish with us

Policies and ethics

Search

Navigation