The Structure of CD4

  • R. L. Brady
  • A. N. Barclay
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 205)

Abstract

The CD4 antigen was first identified by the W3/25 monoclonal antibody (mAb) in the rat and indeed was one of the first lymphocyte cell surface antigens to be defined by monoclonal antibodies in any species (Williams et al. 1977). The W3/25 mAb was of particular interest as it was the first marker for the sub-population of T lymphocytes with “helper” activity (White et al. 1978). The human homologue of the W3/25 antigen was identified with the mAb T4 (Reinherz et al. 1979) and later termed CD4. The CD (clusters of differentiation) nomenclature was introduced as a simple method to group together mAbs that recognised the same antigen at the surface of human leucocytes (Bernard et al. 1984). This nomenclature is now widely used to describe both the antibody recognising the antigen and the antigen itself. It is also used to describe homologues in species other than humans.

Keywords

Sugar Crystallization Hydroxyl Carbohydrate Tyrosine 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Ashford DA, Alafi CD, Gamble VM, Mackay DJ, Rademacher TW, Williams PJ, Dwek RA, Barclay AN, Davis SJ, Somoza C, Ward HA, Williams AF (1993) Site specific glycosylation of recombinant rat and human soluble CD4 variants expressed in Chinese hamster ovary cells. J Biol Chem 268: 3260–3267PubMedGoogle Scholar
  2. Baixeras E, Huard B, Miossec C, Jitsukawa S, Martin M, Hercend T, Auffray C, Triebel F, Piatier TD (1992) Characterization of the lymphocyte activation gene 3-encoded protein. A new ligand for human leukocyte antigen class II antigens. J Exp Med 176: 327–337PubMedCrossRefGoogle Scholar
  3. Barclay AN, Brady RL, Davis SJ, Lange G (1993) CD4 and the immunoglobulin superfamiiy. Philos Trans R Soc Lond Biol 342: 7–12PubMedCrossRefGoogle Scholar
  4. Bernard A, Boumsell L, Dausset J, Milstein C, Schlossman SF (1984) Leucocyte typing. Springer, Berlin Heidelberg New YorkGoogle Scholar
  5. Brady RL, Dodson EJ, Dodson GG, Lange G, Davis SJ, Williams AF, Barclay AN (1993) Crystal structure of domains 3 and 4 of rat CD4; relation to the NH2-terminal domains. Science 260: 979–983PubMedCrossRefGoogle Scholar
  6. Brostoff SW, Mason DW (1984) Experimental allergic encephalomyelitis: successful treatment in vivo with a monoclonal antibody that recognizes T helper cells. J Immunol 133: 1938–1942PubMedGoogle Scholar
  7. Brown JH, Jardetsky TS, Gorga JC, Stem LJ, Urban RG, Strominger JL, Wiley DC (1993) Three-dimensional structure of the human class II histocompatibility antigen HLA-DR1. Nature 364: 33–39PubMedCrossRefGoogle Scholar
  8. Cammarota G, Scheirie A, Takacs B, Doran DM, Knorr R, Bannwarth W, Guardiola J, Sinigaglia F(1992) Identification of a CD4 binding site on the beta 2 domain of HLA-DR molecules. Nature 356: 799–801Google Scholar
  9. Clark SJ, Jefferies WA, Barclay AN, Gagnon J, Williams AF (1987) Peptide and nucleotide sequences of rat CD4 (W3/25) antigen: evidence for derivation from a structure with four immunoglobulin- related domains. Proc Natl Acad Sci USA 84: 1649–1653PubMedCrossRefGoogle Scholar
  10. Dalgleish AG, Beverley PC, Clapham PR, Crawford DH, Greaves MF, Weiss RA (1984) The CD4 (T4) antigen is an essential component of the receptor for the AIDS retrovirus. Nature 312: 763–767PubMedCrossRefGoogle Scholar
  11. Davis SJ, Brady RL, Barclay AN, Harlos K, Dodson GG, Williams AF (1990a) Crystallization of a soluble form of the rat T-cell surface glycoprotein CD4 complexed with Fab from the W3/25 monoclonal antibody. J Mol Biol 213: 7–10PubMedCrossRefGoogle Scholar
  12. Davis SJ, Ward HA, Puklavec MJ, Willis AC, Williams AF, Barclay AN (1990b) High level expression in Chinese hamster ovary cells of soluble forms of CD4 T lymphocyte glycoprotein including glycosylation variants. J Biol Chem 265: 10410–10418PubMedGoogle Scholar
  13. Doyle C, Strominger JL (1987) Interaction between CD4 and class II MHC molecules mediates cell adhesion. Nature 330: 256–259PubMedCrossRefGoogle Scholar
  14. Fomsgaard A, Hirsch VM, Johnson PR(1992) Cloning and sequences of primate CD4 molecules: diversity of the cellular receptor for simian immunodeficiency virus/human immunodeficiency virus. Eur J Immunol 22: 2973–2981Google Scholar
  15. Garrett T, Wang J, Yan Y, Liu J, Harrison SC (1993) Refinement and analysis of the structure of the first two domains of human CD4. J Mol Biol 234: 763–778PubMedCrossRefGoogle Scholar
  16. Harpaz Y, Chothia C (1994) Many of the immunoglobulin superfamily domains in cell adhesion molecules and surface receptors belong to a new structural set which is close to that containing variable domains. J Mol Biol 238: 528–539PubMedCrossRefGoogle Scholar
  17. Houlgatte R, Scarmato P, Marhomy SE, Martin M, Ostankovitch M, Hatosse S, Vervisch A, Auffray C, Platieonnear D (1994) HLA class II antigens and the HIV envelope glycoprotein GP120 bind to the same face of CD4. J Immunol 152: 4475–4488PubMedGoogle Scholar
  18. Hussey RE, Richardson NE, Kowalski M, Brown NR, Chang HC, Siliciano RF, Dorfman T, Walker B, Sodroski J, Reinherz EL (1988) A soluble CD4 protein selectively inhibits HIV replication and syncytium formation. Nature 331: 78–81PubMedCrossRefGoogle Scholar
  19. Jones EY, Davis SJ, Williams AF, Harlos K, Stuart Dl (1992) Crystal structure at 2.8 A resolution of a soluble form of the cell adhesion molecule CD2. Nature 360: 232–239PubMedCrossRefGoogle Scholar
  20. Klatzmann D, Champagne E, Chamare, Gruest J, Guetard D, Hercen, Gluckman JC, Montagnier L (1984) T-lymphocyte T4 molecule behaves as the receptor for human retrovirus LAV. Nature 312: 767–768PubMedCrossRefGoogle Scholar
  21. Kuchel PW, Campbell DG, Barclay AN, Williams AF (1978) Molecular weights of the Thy-1 glycoproteins from rat thymus and brain in the presence and absence of deoxycholate. Biochem J 169: 411–417PubMedGoogle Scholar
  22. Kwong PD, Ryu SE, Hendrickson WA, Axel R, Sweet RM, Falena WG, Hensley P, Sweet RW (1990) Molecular characteristics of recombinant human CD4 as deduced from polymorphic crystals. Proc Natl Acad Sci USA 87: 6423–6427PubMedCrossRefGoogle Scholar
  23. Lange G, Lewis SJ, Murshudov GN, Dodson GG, Moody PCE, Turkenburg JP, Barclay AN, Brady LR (1994) Crystal structure of an extracellular fragment of the rat CD4 receptor containing domains 3 and 4. Structure 2: 469–481PubMedCrossRefGoogle Scholar
  24. Langedijk J, Puijk WC, Van HW, Meloen RH (1993) Location of CD4 dimerization site explains critical role of CDR3-like region in HIV-1 infection and T-cell activation and implies a model for complex of coreceptor-MHC. J Biol Chem 268: 16875–16878PubMedGoogle Scholar
  25. Littman DR (1987) The structure of the CD4 and CD8 genes. Annu Rev Immunol 5: 561–584PubMedCrossRefGoogle Scholar
  26. Maddon PJ, Littman DR, Godfrey M, Maddon DE, Chess L, Axel R (1985) The isolation and nucleotide sequence of a NA encoding the T cell surface protein T4: a new member of the immunoglobulin gene family. Cell 42: 93–104PubMedCrossRefGoogle Scholar
  27. Maddon PJ, Molineaux, SM, Maddon DE, Zimmerman KA, Godfrey M, Alt FW, Chess L, Axel R (1987) Structure and expression of the human and mouse T4 genes. Proc Natl Acad Sci USA 84: 9155–9159PubMedCrossRefGoogle Scholar
  28. Moebius U, Clayton LK, Abraham S, Harrison SC, Reinherz EL (1992) The human immunodeficiency virus gp120 binding site on CD4: Delineation by quantitative equilibrium and kinetic binding studies of mutants in conjunction with a high-resolution CD4 atomic structure. J Exp Med 176: 507–517PubMedCrossRefGoogle Scholar
  29. Nag B, Wada HG, Passmore D, Clark BR, Sharma SD, McConnell HM (1993) Purified beta-chain of MHC Class II binds to CD4 molecules on transfected Ha cells. J Immunol 150: 1358–1364PubMedGoogle Scholar
  30. Pal R, Nair BC, Hoke GM, Sarngadharan MG, Edidin M (1991) Lateral diffusion of CD4 on a human neoplastic T-cell line probed with a fluorescent derivative of the envelope glycoprotein (gp120) of human immunodeficiency virus type 1 (HIV-1). J Cell Physiol 147: 326–332PubMedCrossRefGoogle Scholar
  31. Reinherz EL, Kung PC, Goldstein G, Schlossman SF (1979) Separation of functional subsets of human T cells by a monoclonal antibody. Proc Natl Acad Sci USA 76: 4061–4065PubMedCrossRefGoogle Scholar
  32. Rudd CE, Trevillyan JM, Dasgupta JD, Wong LL, Schlossman SF (1988) The CD4 receptor is complexed in detergent lysates to a protein-tyrosine kinase (pp58) from human T lymphocytes. Proc Natl Acad Sci USA 85: 5190–5194PubMedCrossRefGoogle Scholar
  33. Ryu SE, Kwong PD, Truneh A, Porter TG, Arthos J, Rosenberg M, Dai XP, Xuong NH, Axel R, Sweet RW et al. (1990) Crystal structure of an HIV-binding recombinant fragment of human CD4. Nature 348: 419–426PubMedCrossRefGoogle Scholar
  34. Ryu SE, Truneh A, Sweet RW, Hendrickson WA (1994) Structures of an HIV and MHC binding fragment from human CD4 as refined in two crystal lattices. Structure 2: 59–74PubMedCrossRefGoogle Scholar
  35. Schockmel GA, Somoza C, Davis SJ, Williams AF, Healey D (1992) Construction of a binding site for human immunodeficiency virus type 1 gp120 in rat CD4. J Exp Med 175: 301–304PubMedCrossRefGoogle Scholar
  36. Spellman MW, Leonard CK, Basa LJ, Gelineo I, Van HH (1991) Carbohydrate structures of recombinant soluble human CD4 expressed in Chinese hamster ovary cells. Biochemistry 30: 2395–2406PubMedCrossRefGoogle Scholar
  37. Triebel F, Jitsukawa S, Baixeras E, Roman RS, Genevee C, Viegals PE, Hercend T (1990) LAG-3, a novel lymphocyte activation gene closely related to CD4. J Exp Med 171: 1393–1405PubMedCrossRefGoogle Scholar
  38. Tsui P, Sweet RW, Sathe G, Rosenberg M (1992) An efficient phage plaque screen for the random mutational analysis of the interaction of HIV-1 gp120 with human CD4. J Biol Chem 267: 9361–9367PubMedGoogle Scholar
  39. van der Merwe PA, Brown MH, Davis SJ, Barclay AN (1993) Affinity and kinetic analysis of the interaction of the cell-adhesion molecules rat CD2 and CD48. EMBO J 12: 4945–4954PubMedGoogle Scholar
  40. Veillette A, Sleckman BP, Ratnofsky S, Bolen JB, Burakoff SJ (1990) The cytoplasmic domain of CD4 is required for stable association with the lymphocyte-specific tyrosine protein kinase p56lck. Eur J Immunol 20: 1397–1400PubMedCrossRefGoogle Scholar
  41. Vignali DAA, Doyle C, Kinch MS, Shin J, Strominger JL (1993) Interactions of CD4 with MHC class II molecules, T cell receptors and p56lck. Phil Trans R Soc Lond B 342: 13–24CrossRefGoogle Scholar
  42. Wang JH, Yan YW, Garrett TP, Liu JH, Rodgers DW, Garlick RL, Tarr GE, Husain Y, Reinherz EL, Harrison SC (1990) Atomic structure of a fragment of human CD4 containing two immunoglobulin- like domains. Nature 348: 411–418PubMedCrossRefGoogle Scholar
  43. Webb M, Mason DW, Williams AF (1979) Inhibition of mixed lymphocyte response by monoclonal antibody specific for a rat T lymphocyte subset. Nature 282: 841–843PubMedCrossRefGoogle Scholar
  44. Weber S, Karjalainen K (1993) Mouse CD4 binds MHC class II with extremely low affinity. Int Immunol 5: 695–698PubMedCrossRefGoogle Scholar
  45. White RA, Mason DW, Williams AF, Galfre G, Milstein C (1978) T-lymphocyte heterogeneity in the rat-separation of functional subpopulations using a monoclonal antibody. J Exp Med 148: 664–673PubMedCrossRefGoogle Scholar
  46. Williams AF, Barclay AN (19£8) The immunoglobulin superfamily—domains for cell surface recognition. Annu Rev Immunol 6: 381–405Google Scholar
  47. Williams AF, Galfre G, Milstein C (1977) Analysis of cell surfaces by xenogeneic myeloma-hybrid antibodies: differentiation antigens of rat lymphocytes. Cell 12: 663–673PubMedCrossRefGoogle Scholar
  48. Williams AF, Davis SJ, He Q, Barclay AN (1989) Structural diversity in domains of the immunoglobulin superfamily.Cold Spring Harb Symp Quant Biol LIV: 637–647Google Scholar
  49. Yuen CT, Carr SA, Feizi T (1990) The spectrum of N-linked oligosaccharide structures detected by enzymic microsequencing on a recombinant soluble CD4 glycoprotein from Chinese hamster ovary cells. Eur J Biochem 192: 523–528PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1996

Authors and Affiliations

  • R. L. Brady
    • 1
  • A. N. Barclay
    • 2
  1. 1.Department of BiochemistryUniversity of BristolBristolUK
  2. 2.MRC Cellular Immunology Unit, Sir William Dunn School of PathologyUniversity of OxfordOxfordUK

Personalised recommendations