Advertisement

Immunologic Research

, Volume 19, Issue 2–3, pp 201–210 | Cite as

Molecular analysis of protein interactions mediating the function of the cell surface protein CD8

  • Lesley Devine
  • Paula B. Kavathas
Article

Abstract

The T cell coreceptor CD8 is a cell-surface glycoprotein expressed either as a disulfide-linked homodimer of two CD8α monomers, or a heterodimer of CD8α and CD8Β. These receptors interact with ligands, such as major histocompatibility complex (MHC) class I, on the outside of the cell, with proteins inside the cell, such as the tyrosine kinase p56lck, and possibly with proteins on the same cellsurface. The molecular details describing such protein interactions can shed light on how the proteins function and the functional differences between the two forms of CD8. Crystal structures, mutational analysis, affinity measurements, and other approaches are providing those details.

Keywords

T lymphocytes MHC Cell surface molecule Adhesion 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Cantor H, Boyse EA: Lymphocytes as models for the study of mammalian cellular differentiation. Immunol Rev 1977;33: 105–124.PubMedCrossRefGoogle Scholar
  2. 2.
    Kavathas P, Sukhatme VP, Her-zenberg LA, Parnes JR: Isolation of the gene encoding the human T-lymphocyte differentiation antigen Leu-2 (T8) by gene transfer and cDNA subtraction. Proc Natl Acad Sci U S A 1984;81(24): 7688–92.PubMedCrossRefGoogle Scholar
  3. 3.
    Littman DR, Thomas Y, Maddon PJ, Chess L, Axel R: The isolation and sequence of the gene encoding T8: a molecule defining functional classes of T lymphocytes. Cell. 1985;40:237–246.PubMedCrossRefGoogle Scholar
  4. 4.
    Johnson P, Williams AF: Striking similarities between antigen receptor J pieces and sequence in the second chain of the murine CD8 antigen. Nature 1986;323: 74–76.PubMedCrossRefGoogle Scholar
  5. 5.
    Gabert J, Langlet C, Zamoyska R, Parnes JR, Schmitt-Verhulst AM, Malissen B: Reconstitution of MHC class I specificity by transfer of the T cell receptor and Lyt2 genes. Cell 1987;50:545–554.PubMedCrossRefGoogle Scholar
  6. 6.
    Norment AM, Salter RD, Parham P, Engelhard VH, Littman DR: Cell-cell adhesion mediated by CD8 and MHC class I molecules. Nature 1988;336:79–81.PubMedCrossRefGoogle Scholar
  7. 7.
    Swain SL: T cell subsets and the recognition of MHC class. Immunol Rev 1983;74:129–142.PubMedCrossRefGoogle Scholar
  8. 8.
    Fung-Leung W-P, Schilham MW, Rahemtulla A, Kundig TM, Vollenweider M, Potter J, et al.: CD8 is needed for development of cytotoxic T cells but not for helper T cells. Cell 1991;65:443–449.PubMedCrossRefGoogle Scholar
  9. 9.
    Crooks ME, Littman DR: Disruption of T lymphocyte positive and negative selection in mice lacking the CD8Β chain. Immunity 1994; 1:277–285.PubMedCrossRefGoogle Scholar
  10. 10.
    Fung-Leung W-P, Kundig TM, Ngo K, Panakos J, De Sousa-Hitzler J, Mak TW, et al.: Reduced thymic maturation but normal effector function of CD8+ T cells in CD8Β gene-targeted mice. J Exp Med 1994;180:959–967.PubMedCrossRefGoogle Scholar
  11. 11.
    Barber EK, Dasgupta JD, Schloss-man SF, Trevillyan JM, Rudd CE: The CD4 and CD8 antigens are coupled to a protein-tyrosine kinase (p561ck) that phosphorylates the CD3 complex. Proc Natl Acad Sci USA 1989;86:3277–3281.PubMedCrossRefGoogle Scholar
  12. 12.
    Veillette A, Bookman MA, Horak EM, Bolen JB: The CD4 and CD8 T cell surface antigens are associated with the internal membrane tyrosine-protein kinase p561ck. Cell 1988;55:301–308.PubMedCrossRefGoogle Scholar
  13. 13.
    Connolly JM, Hansen TH, Ingold AI, Potter TA: Recognition by CD8 on cytotoxic T lymphocytes is ablated by several substitutions in the class I α3 domain: CD8 and the T cell receptor recognize the same class I molecule. Proc Natl Acad Sci USA 1990;87:2137–2141.PubMedCrossRefGoogle Scholar
  14. 14.
    Salter RD, Benjamin RJ, Wesley PK, Buxton SE, Garrett TPJ, Clayberger C, et al.: A binding site for the T-cell co-receptor CD8 on the α3 domain of HLA-A2. Nature 1990;345:41–46.PubMedCrossRefGoogle Scholar
  15. 15.
    Leahy DJ, Axel R, Hendrickson WA: Crystal structure of a soluble form of the human T cell coreceptor CD8 at 2.6 å resolution. Cell 1992;68:1145–1162.PubMedCrossRefGoogle Scholar
  16. 16.
    Sanders SK, Fox RO, Kavathas P: Mutations in CD8 that affect interactions with HLA class I and monclonal anti-CD8 antibodies. J Exp.Med 1991;174:371–379.PubMedCrossRefGoogle Scholar
  17. 17.
    Giblin PA, Leahy DJ, Mennone J, Kavathas PB: The role of charge and multiple faces of the CD8α/α homodimer in binding to major histocompatibility complex class I molecules: support for a bivalent model. Proc Natl Acad Sci USA 1994;91:1716–1720.PubMedCrossRefGoogle Scholar
  18. 18.
    Sun J, Leahy DJ, Kavathas PB: Interaction between CD8 and MHC class I mediated by multiple contact surfaces that include the α2 and a3 domains of MHC class I. J Exp Med 1995;182:1275–1280.PubMedCrossRefGoogle Scholar
  19. 19.
    Gao GF, Tormo J, Gerth UC, Wyer JR, McMichael AJ, Stuart DI, et al.: Crystal structure of the complex between human CD8αα and HLAA2. Nature 1997;387:630–634.PubMedCrossRefGoogle Scholar
  20. 20.
    Kern PS, Teng M-K, Smolyar A, Liu J, Hussey RE, Spoerl R, et al.: Structural basis of CD8 coreceptor function revealed by crystallographic analysis of a murine CD8αα ectodomain fragment in complex with H-2Kb. Immunity 1998;9:519–530.PubMedCrossRefGoogle Scholar
  21. 21.
    O’Rourke AM, Rogers J, Mescher MF: Activated CD8 binding to class I protein mediated by the T cell receptor results in signalling. Nature 1990;346:187–189.PubMedCrossRefGoogle Scholar
  22. 22.
    Shen L, Potter TA, Kane KP: Glu227→Lys substitution in the acidic loop of major histocompatibility complex class I alpha 3 domain distinguishes low avidity CD8 coreceptor and avidity enhanced CD8 accessory functions. J Exp Med 1996; 184: 1671–1683.PubMedCrossRefGoogle Scholar
  23. 23.
    Karaki S, Tanabe M, Nakauchi H, Takiguchi M: Β-chain broadens range of CD8 recognition for MHC class I molecule. J Immunol 1992;149:1613–1618.PubMedGoogle Scholar
  24. 24.
    Wheeler CJ, von Hoegen P, Parnes JR: An immunological role for the CD8 beta chain. Nature 1992;357: 247–249.PubMedCrossRefGoogle Scholar
  25. 25.
    Garcia KC, Scott CA, Brunmark A, Carbone FR, Peterson PA, Wilson IA, et al.: CD8 enhances formation of stable T-cell receptor/ MHC class I molecule complexes. Nature 1996;384:577–581.PubMedCrossRefGoogle Scholar
  26. 26.
    Sun J, Kavathas PB: Comparison of the roles of CD8αα and CD8αΒ in interaction with MHC class I. J Immunol 1997;159:6077–6082.PubMedGoogle Scholar
  27. 27.
    Devine L, Sun J, Barr MR, Kavathas PB: Orientation of the Ig domains of CD8αΒ relative to MHC class I J Immunol 1999; 162:846–851.PubMedGoogle Scholar
  28. 28.
    Shaw AS, Chalupny J, Whitney JA, Hammond C, Amrein KE, Kavathas P, et al.: Short related sequences in the cytoplasmic domains of CD4 and CD8 mediate binding to the amino-terminal domain of the p56lck tyrosine protein kinase. Mol Cell Biol 1990;10:1853–1862.PubMedGoogle Scholar
  29. 29.
    Turner JM, Brodsky MH, Irving BA, Levin SD, Perlmutter RM, Littman DR: Interaction of the unique N-terminal region of tyrosine kinase p56lck with cytoplasmic domains of CD4 and CD8 is mediated by cysteine motifs. Cell 1990;60:755–765.PubMedCrossRefGoogle Scholar
  30. 30.
    Irie HY, Mong MS, Itano A, Crooks ME, Littman DR, Burakoff SJ, etal.: The cytoplasmic domain of CD8 beta regulates Lck kinase activation and CD8 T cell development. J Immunol 1998;161:183–191.PubMedGoogle Scholar
  31. 31.
    Irie HY, Ravichandran KS, Bura-koff SJ: CD8Β chain influences CD8α chain-associated Lck kinase activity. J Exp Med 1995; 181:1267–1273.PubMedCrossRefGoogle Scholar
  32. 32.
    Itano A, Cado D, Chan FKM, Robey E: A role for the cytoplasmic tail of the CD8Β chain of CD8 in thymic selection. Immunity 1994;1:287–290.PubMedCrossRefGoogle Scholar
  33. 33.
    Boyce NW, Jonsson JI, Emmrich F, Eichmann K: Heterologous cross-linking of Lyt-2 (CD8) to the alpha beta-T cell receptor is more effective in T cell activation than homologous alpha beta-T cell receptor cross-linking. J Immunol 1988;141:2882–2888.PubMedGoogle Scholar
  34. 34.
    Ledbetter JA, Norris NA, Gross-mann A, Grosmaire LS, June CH, Uckun FM, et al.: Enhanced transmembrane signalling activity of monoclonal antibody heteroconjugates suggests molecular interactions between receptors on the T cell surface. Mol Immunol 1989; 26:137–145.PubMedCrossRefGoogle Scholar
  35. 35.
    Renard V, Romero P, Vivier E, Malissen B, Leuscher IF: CD8Β increases CD8 co-receptor function and participation in TCRligand binding. J Exp Med 1996; 184:2439–2444.PubMedCrossRefGoogle Scholar
  36. 36.
    Lim G-EK, McNeill L, Whitely K, Becker DL, Zamoyska R: Cocapping studies reveal CD8/TCR interactions after capping CD8Β polypeptides and intracellular associations of CD8 with p56lck. Eur. J Immunol 1998;28:745–754.CrossRefGoogle Scholar
  37. 37.
    Arden B: Conserved motifs in T-cell receptor CDR1 and CDR2: implications for ligand and CD8 co-receptor binding. Curr Opinion Immunol 1998;10:74–81.CrossRefGoogle Scholar
  38. 38.
    Classon BJ, Brown MH, Garnett D, Somoza C, Barclay AN, Willis AC, et al.: The hinge region of the CD8α chain: structure, antigenicity, and utility in expression of immunoglobulin superfamily domains. Int Immunol 1992;4: 215–225.PubMedCrossRefGoogle Scholar
  39. 39.
    Casabo LG, Mamalaki C, Kioussis D, Zamoyska R: T cell activation results in physical modification of the mouse CD8Β chain. J Immunol 1994; 152:397–404.PubMedGoogle Scholar
  40. 40.
    Sanders S, Giblin PA, Kavathas P: Cell-cell adhesion mediated by CD8 and human histocompatability leukocyte antigen G, a nonclassical major histocompatibility complex class I molecule on cytotrophoblasts. J Exp Med 1991; 174:737–740.PubMedCrossRefGoogle Scholar
  41. 41.
    Teitell M, Mescher MF, Olson CA, Littman DR, Kronenberg M: The thymus leukemia antigen binds human and mouse CD8. J Exp Med 1991;174:1131–1138.PubMedCrossRefGoogle Scholar
  42. 42.
    Yio XY, Mayer L: Characterization of a gp180-kDa intestinal epithelial cell membrane glycoprotein, gp 180. J Biol Chem 1997; 272:12,786–12,792.CrossRefGoogle Scholar
  43. 43.
    Li Y, Yio XY, Mayer L: Human intestinal epithelial cell-induced CD8+ T cell activation is medioated through CD8 and the activation of CD8-associated p56lck. J Exp Med 1995;182: 1079–1088.PubMedCrossRefGoogle Scholar
  44. 44.
    Olsson T, Bakhiet M, Hojeberg B, Ljungdahl A, Edlund C, Andersson G, et al.: CD8 is critically involved in lymphocyte activation by a T brucei-released molecule. Cell 1993;72:715–727.PubMedCrossRefGoogle Scholar
  45. 45.
    Vaidya T, Bakhiet M, Hill KL, Olsson T, Kristensson K, Donel-son JE: The gene for a T lymphocyte triggering factor from african trypanosomes. J Exp Med 1997; 186:433–437.PubMedCrossRefGoogle Scholar
  46. 46.
    Porcelli SA, Segelke BW, Sugita M, Wilson IA, Brenner MB: The CD1 family of lipid antigenpresenting molecules. Immunol Today 1998;19:362–367.PubMedCrossRefGoogle Scholar
  47. 47.
    Vremec D, Shortman K: Dendritic cell subtypes in mouse lymphoid organs: cross-correlation of surface markers, changes with incubation, and differences among thymus, spleen, and lymph nodes. J Immunol 1997;159:565–573.PubMedGoogle Scholar
  48. 48.
    Lin T-J, Hirji N, Nohara O, Stenton GR, Gilchrist M, Befus AD: Mast cells express novel CD8 molecules that selectively modualte mediator secretion. J Immunol 1998; 161: 6265–6272.PubMedGoogle Scholar
  49. 49.
    Jarry A, Cerf-Bensussan N, Brousse N, Selz F, Guy-Grand D: Subsets of CD3+ (T cell receptor αΒ or γδ) and CD3- lymphocytes isolated from normal human epithelium display phenotypical features different from their counterparts in peripheral blood. Eur J Immunol 1990;1990: 1097–1103.CrossRefGoogle Scholar
  50. 50.
    Hercend Y, Reinherz EL, Meuer S, Schlossmann SF, Ritz J: Phenotypic and functional heterogeneity of human cloned natural killer cell. Nature 1983;301:158–160.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc. 1999

Authors and Affiliations

  • Lesley Devine
  • Paula B. Kavathas
    • 1
    • 2
  1. 1.Department of Laboratory Medicine and Section of ImmunobiologyYale University School of MedicineNew Haven
  2. 2.Department of GeneticsYale University School of MedicineNew Haven

Personalised recommendations