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. 1993 Aug 1;178(2):549–558. doi: 10.1084/jem.178.2.549

Mutational analysis of the CD2/CD58 interaction: the binding site for CD58 lies on one face of the first domain of human CD2

PMCID: PMC2191138  PMID: 7688025

Abstract

The adhesion interaction between the immunoglobulin superfamily molecules CD2 and CD58 (lymphocyte function-associated antigen 3) plays an important role in T cell and natural killer cell interaction with various antigen-presenting and target cells. Determination of the solution structure of rat CD2 domain 1 has allowed a model of human CD2 domain 1 to be generated, and a series of mutants based on this model have been made. Residues of domain 1 of human CD2 predicted to be solvent exposed were substituted with the equivalent residues present in the rat CD2 molecule. The ability of these mutants to mediate rosetting with human and sheep erythrocytes was studied. Results show that the binding site of CD2 for both human and sheep CD58 maps to the beta sheet containing beta strands CC'C"F and G. Residues K34 and E36 in beta strand C, R48 and K49 in beta strand C', and K91 and N92 in the loop connecting beta strands F and G are shown to be critical in the interaction. The data support the proposition that the interaction between CD2 and CD58 involves the major beta sheet face of CD2.

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Selected References

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  1. Beyers A. D., Barclay A. N., Law D. A., He Q., Williams A. F. Activation of T lymphocytes via monoclonal antibodies against rat cell surface antigens with particular reference to CD2 antigen. Immunol Rev. 1989 Oct;111:59–77. doi: 10.1111/j.1600-065x.1989.tb00542.x. [DOI] [PubMed] [Google Scholar]
  2. Beyers A. D., Davis S. J., Cantrell D. A., Izquierdo M., Williams A. F. Autonomous roles for the cytoplasmic domains of the CD2 and CD4 T cell surface antigens. EMBO J. 1991 Feb;10(2):377–385. doi: 10.1002/j.1460-2075.1991.tb07959.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Beyers A. D., Spruyt L. L., Williams A. F. Molecular associations between the T-lymphocyte antigen receptor complex and the surface antigens CD2, CD4, or CD8 and CD5. Proc Natl Acad Sci U S A. 1992 Apr 1;89(7):2945–2949. doi: 10.1073/pnas.89.7.2945. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bierer B. E., Peterson A., Barbosa J., Seed B., Burakoff S. J. Expression of the T-cell surface molecule CD2 and an epitope-loss CD2 mutant to define the role of lymphocyte function-associated antigen 3 (LFA-3) in T-cell activation. Proc Natl Acad Sci U S A. 1988 Feb;85(4):1194–1198. doi: 10.1073/pnas.85.4.1194. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bockenstedt L. K., Goldsmith M. A., Dustin M., Olive D., Springer T. A., Weiss A. The CD2 ligand LFA-3 activates T cells but depends on the expression and function of the antigen receptor. J Immunol. 1988 Sep 15;141(6):1904–1911. [PubMed] [Google Scholar]
  6. Brown M. H., Gorman P. A., Sewell W. A., Spurr N. K., Sheer D., Crumpton M. J. The gene coding for the human T-lymphocyte CD2 antigen is located on chromosome 1p. Hum Genet. 1987 Jun;76(2):191–195. doi: 10.1007/BF00284920. [DOI] [PubMed] [Google Scholar]
  7. Cammarota G., Scheirle A., Takacs B., Doran D. M., Knorr R., Bannwarth W., Guardiola J., Sinigaglia F. Identification of a CD4 binding site on the beta 2 domain of HLA-DR molecules. Nature. 1992 Apr 30;356(6372):799–801. doi: 10.1038/356799a0. [DOI] [PubMed] [Google Scholar]
  8. Deckert M., Kubar J., Zoccola D., Bernard-Pomier G., Angelisova P., Horejsi V., Bernard A. CD59 molecule: a second ligand for CD2 in T cell adhesion. Eur J Immunol. 1992 Nov;22(11):2943–2947. doi: 10.1002/eji.1830221128. [DOI] [PubMed] [Google Scholar]
  9. Driscoll P. C., Cyster J. G., Campbell I. D., Williams A. F. Structure of domain 1 of rat T lymphocyte CD2 antigen. Nature. 1991 Oct 24;353(6346):762–765. doi: 10.1038/353762a0. [DOI] [PubMed] [Google Scholar]
  10. Elliott J. F., Albrecht G. R., Gilladoga A., Handunnetti S. M., Neequaye J., Lallinger G., Minjas J. N., Howard R. J. Genes for Plasmodium falciparum surface antigens cloned by expression in COS cells. Proc Natl Acad Sci U S A. 1990 Aug;87(16):6363–6367. doi: 10.1073/pnas.87.16.6363. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Fleury S., Lamarre D., Meloche S., Ryu S. E., Cantin C., Hendrickson W. A., Sekaly R. P. Mutational analysis of the interaction between CD4 and class II MHC: class II antigens contact CD4 on a surface opposite the gp120-binding site. Cell. 1991 Sep 6;66(5):1037–1049. doi: 10.1016/0092-8674(91)90447-7. [DOI] [PubMed] [Google Scholar]
  12. Fröland S. S. Binding of sheep erythrocytes to human lymphocytes. A probable marker of T lymphocytes. Scand J Immunol. 1972;1(3):269–280. doi: 10.1111/j.1365-3083.1972.tb01818.x. [DOI] [PubMed] [Google Scholar]
  13. He Q., Beyers A. D., Barclay A. N., Williams A. F. A role in transmembrane signaling for the cytoplasmic domain of the CD2 T lymphocyte surface antigen. Cell. 1988 Sep 23;54(7):979–984. doi: 10.1016/0092-8674(88)90112-2. [DOI] [PubMed] [Google Scholar]
  14. Holter W., Fischer G. F., Majdic O., Stockinger H., Knapp W. T cell stimulation via the erythrocyte receptor. Synergism between monoclonal antibodies and phorbol myristate acetate without changes of free cytoplasmic Ca++ levels. J Exp Med. 1986 Mar 1;163(3):654–664. doi: 10.1084/jem.163.3.654. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Hünig T., Tiefenthaler G., Meyer zum Büschenfelde K. H., Meuer S. C. Alternative pathway activation of T cells by binding of CD2 to its cell-surface ligand. Nature. 1987 Mar 19;326(6110):298–301. doi: 10.1038/326298a0. [DOI] [PubMed] [Google Scholar]
  16. Jones E. Y., Davis S. J., Williams A. F., Harlos K., Stuart D. I. Crystal structure at 2.8 A resolution of a soluble form of the cell adhesion molecule CD2. Nature. 1992 Nov 19;360(6401):232–239. doi: 10.1038/360232a0. [DOI] [PubMed] [Google Scholar]
  17. Kato K., Koyanagi M., Okada H., Takanashi T., Wong Y. W., Williams A. F., Okumura K., Yagita H. CD48 is a counter-receptor for mouse CD2 and is involved in T cell activation. J Exp Med. 1992 Nov 1;176(5):1241–1249. doi: 10.1084/jem.176.5.1241. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Katz F. E., Janossy G., Cumber A., Ross W., Blacklock H. A., Tax W., Thorpe P. E. Elimination of T cells from human peripheral blood and bone marrow using a cocktail of three anti-T cell immunotoxins. Br J Haematol. 1987 Dec;67(4):407–411. doi: 10.1111/j.1365-2141.1987.tb06161.x. [DOI] [PubMed] [Google Scholar]
  19. Killeen N., Moessner R., Arvieux J., Willis A., Williams A. F. The MRC OX-45 antigen of rat leukocytes and endothelium is in a subset of the immunoglobulin superfamily with CD2, LFA-3 and carcinoembryonic antigens. EMBO J. 1988 Oct;7(10):3087–3091. doi: 10.1002/j.1460-2075.1988.tb03174.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Krensky A. M., Robbins E., Springer T. A., Burakoff S. J. LFA-1, LFA-2, and LFA-3 antigens are involved in CTL-target conjugation. J Immunol. 1984 May;132(5):2180–2182. [PubMed] [Google Scholar]
  21. Leahy D. J., Axel R., Hendrickson W. A. Crystal structure of a soluble form of the human T cell coreceptor CD8 at 2.6 A resolution. Cell. 1992 Mar 20;68(6):1145–1162. doi: 10.1016/0092-8674(92)90085-q. [DOI] [PubMed] [Google Scholar]
  22. Martin D. R., Yuryev A., Kalli K. R., Fearon D. T., Ahearn J. M. Determination of the structural basis for selective binding of Epstein-Barr virus to human complement receptor type 2. J Exp Med. 1991 Dec 1;174(6):1299–1311. doi: 10.1084/jem.174.6.1299. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Meuer S. C., Hussey R. E., Fabbi M., Fox D., Acuto O., Fitzgerald K. A., Hodgdon J. C., Protentis J. P., Schlossman S. F., Reinherz E. L. An alternative pathway of T-cell activation: a functional role for the 50 kd T11 sheep erythrocyte receptor protein. Cell. 1984 Apr;36(4):897–906. doi: 10.1016/0092-8674(84)90039-4. [DOI] [PubMed] [Google Scholar]
  24. Palacios R., Martinez-Maza O. Is the E receptor on human T lymphocytes a "negative signal receptor"? J Immunol. 1982 Dec;129(6):2479–2485. [PubMed] [Google Scholar]
  25. Peterson A., Seed B. Monoclonal antibody and ligand binding sites of the T cell erythrocyte receptor (CD2). 1987 Oct 29-Nov 4Nature. 329(6142):842–846. doi: 10.1038/329842a0. [DOI] [PubMed] [Google Scholar]
  26. Plunkett M. L., Sanders M. E., Selvaraj P., Dustin M. L., Springer T. A. Rosetting of activated human T lymphocytes with autologous erythrocytes. Definition of the receptor and ligand molecules as CD2 and lymphocyte function-associated antigen 3 (LFA-3). J Exp Med. 1987 Mar 1;165(3):664–676. doi: 10.1084/jem.165.3.664. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Pullen A. M., Bill J., Kubo R. T., Marrack P., Kappler J. W. Analysis of the interaction site for the self superantigen Mls-1a on T cell receptor V beta. J Exp Med. 1991 May 1;173(5):1183–1192. doi: 10.1084/jem.173.5.1183. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Recny M. A., Neidhardt E. A., Sayre P. H., Ciardelli T. L., Reinherz E. L. Structural and functional characterization of the CD2 immunoadhesion domain. Evidence for inclusion of CD2 in an alpha-beta protein folding class. J Biol Chem. 1990 May 25;265(15):8542–8549. [PubMed] [Google Scholar]
  29. Sanders S. K., Fox R. O., Kavathas P. Mutations in CD8 that affect interactions with HLA class I and monoclonal anti-CD8 antibodies. J Exp Med. 1991 Aug 1;174(2):371–379. doi: 10.1084/jem.174.2.371. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Seed B. An LFA-3 cDNA encodes a phospholipid-linked membrane protein homologous to its receptor CD2. 1987 Oct 29-Nov 4Nature. 329(6142):840–842. doi: 10.1038/329840a0. [DOI] [PubMed] [Google Scholar]
  31. Seed B., Aruffo A. Molecular cloning of the CD2 antigen, the T-cell erythrocyte receptor, by a rapid immunoselection procedure. Proc Natl Acad Sci U S A. 1987 May;84(10):3365–3369. doi: 10.1073/pnas.84.10.3365. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Selvaraj P., Plunkett M. L., Dustin M., Sanders M. E., Shaw S., Springer T. A. The T lymphocyte glycoprotein CD2 binds the cell surface ligand LFA-3. 1987 Mar 26-Apr 1Nature. 326(6111):400–403. doi: 10.1038/326400a0. [DOI] [PubMed] [Google Scholar]
  33. Siliciano R. F., Pratt J. C., Schmidt R. E., Ritz J., Reinherz E. L. Activation of cytolytic T lymphocyte and natural killer cell function through the T11 sheep erythrocyte binding protein. Nature. 1985 Oct 3;317(6036):428–430. doi: 10.1038/317428a0. [DOI] [PubMed] [Google Scholar]
  34. Springer T. A. Cell adhesion. A birth certificate for CD2. Nature. 1991 Oct 24;353(6346):704–705. doi: 10.1038/353704a0. [DOI] [PubMed] [Google Scholar]
  35. Spruyt L. L., Glennie M. J., Beyers A. D., Williams A. F. Signal transduction by the CD2 antigen in T cells and natural killer cells: requirement for expression of a functional T cell receptor or binding of antibody Fc to the Fc receptor, Fc gamma RIIIA (CD16). J Exp Med. 1991 Dec 1;174(6):1407–1415. doi: 10.1084/jem.174.6.1407. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Staunton D. E., Dustin M. L., Erickson H. P., Springer T. A. The arrangement of the immunoglobulin-like domains of ICAM-1 and the binding sites for LFA-1 and rhinovirus. Cell. 1990 Apr 20;61(2):243–254. doi: 10.1016/0092-8674(90)90805-o. [DOI] [PubMed] [Google Scholar]
  37. Tadmori W., Reed J. C., Nowell P. C., Kamoun M. Functional properties of the 50 kd protein associated with the E-receptor on human T lymphocytes: suppression of IL 2 production by anti-p50 monoclonal antibodies. J Immunol. 1985 Mar;134(3):1709–1716. [PubMed] [Google Scholar]
  38. Tiefenthaler G., Hünig T., Dustin M. L., Springer T. A., Meuer S. C. Purified lymphocyte function-associated antigen-3 and T11 target structure are active in CD2-mediated T cell stimulation. Eur J Immunol. 1987 Dec;17(12):1847–1850. doi: 10.1002/eji.1830171227. [DOI] [PubMed] [Google Scholar]
  39. Williams A. F., Barclay A. N., Clark S. J., Paterson D. J., Willis A. C. Similarities in sequences and cellular expression between rat CD2 and CD4 antigens. J Exp Med. 1987 Feb 1;165(2):368–380. doi: 10.1084/jem.165.2.368. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Williams A. F., Davis S. J., He Q., Barclay A. N. Structural diversity in domains of the immunoglobulin superfamily. Cold Spring Harb Symp Quant Biol. 1989;54(Pt 2):637–647. doi: 10.1101/sqb.1989.054.01.075. [DOI] [PubMed] [Google Scholar]
  41. Wolff H. L., Burakoff S. J., Bierer B. E. Functional CD2 mutants unable to bind to, or be stimulated by, LFA-3. J Immunol. 1990 Feb 15;144(4):1215–1220. [PubMed] [Google Scholar]
  42. Wong Y. W., Williams A. F., Kingsmore S. F., Seldin M. F. Structure, expression, and genetic linkage of the mouse BCM1 (OX45 or Blast-1) antigen. Evidence for genetic duplication giving rise to the BCM1 region on mouse chromosome 1 and the CD2/LFA3 region on mouse chromosome 3. J Exp Med. 1990 Jun 1;171(6):2115–2130. doi: 10.1084/jem.171.6.2115. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Yang S. Y., Chouaib S., Dupont B. A common pathway for T lymphocyte activation involving both the CD3-Ti complex and CD2 sheep erythrocyte receptor determinants. J Immunol. 1986 Aug 15;137(4):1097–1100. [PubMed] [Google Scholar]
  44. Yokota T., Lee F., Rennick D., Hall C., Arai N., Mosmann T., Nabel G., Cantor H., Arai K. Isolation and characterization of a mouse cDNA clone that expresses mast-cell growth-factor activity in monkey cells. Proc Natl Acad Sci U S A. 1984 Feb;81(4):1070–1074. doi: 10.1073/pnas.81.4.1070. [DOI] [PMC free article] [PubMed] [Google Scholar]

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