Abstract
We have developed a cellular adhesion assay in which B lymphocytes expressing HLA class II antigens form rosettes with COS cells expressing high levels of cell surface CD4 upon transient transfection with a CDM8-CD4 plasmid construct. The assay is specific, quantitative, and overcomes the difficulties encountered with a previously described system using an SV40 viral vector. Rosette formation was inhibited by a series of CD4- and HLA-DR-specific antibodies, as well as by human immunodeficiency virus (HIV) gp 120, and a synthetic peptide derived from part of its binding site for CD4 (amino acid residues 414-434), but not by a variety of other effectors, including several soluble CD4 derivatives. The comparison of this pattern of inhibition with those observed in other systems further emphasizes the great similarity, but incomplete identity, in the CD4 binding sites for HLA class II antigens and HIV gp120, and supports a model in which CD4 is considered as an allosteric servomodulator of T-cell adhesion and function which probably is induced to interact with HLA class II antigens when associated with the Tcr/CD3 complex.
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Accolla, R. S.: Human B cell variants immunoselected against a single Ia antigen subset have lost expression of several Ia antigen subsets. J Exp Med 157: 1053–1058, 1983
Ashkenazy, A., Presta, L. G., Marster, S. A., Camerato, T. R., Rosenthal, K. A., Fendly, B. M., and Capon, D. J.: Mapping the CD4 binding site for human immunodeficiency virus by alanin-scanning mutagenesis. Proc Natl Acad Sci USA 87: 7150–7154, 1990
Auffray, C., Piatier-Tonneau, D., and Kroemer, G.: CD4-targeted immune intervention. A strategy for the theraphy of AIDS and autoimmune disease. Trends Biotechnol 9: 124–131, 1991
Barnstable, C. J., Bodmer, W. F., Brown, G., Gaffre, G., Millstein, C., Williams, A. F., and Ziegler, A.: Production of monoclonal antibodies to group A erythrocytes, HLA and other human cell surface antigens. New Tools for genetics analysis Cell 14: 9–13, 1978
Bierer, B. F., Sleckman, B. P., Ranofsky, S. E., and Burakoff, S. J.: The biologic roles of CD2, CD4 and CD8 in T-cell. Ann Rev Immunol 7: 579–599, 1989
Blanchard, D., Vans Els., C., Borst, J., Carrel, S., Boylston, A., De Vries, J. E., and Spits, H.: The role of the T cell receptor, CD8 and LFA1 in different stages of the cytolytic reaction mediated by alloreactive T lymphocyte clones. J Immunol 138: 2417–2421, 1987
Carrel, S., Moretta, A., Pantaleo, G., Tambussi, G., Isler, P., Perussia, B., and Cerottini, J. C.: Stimulation and proliferation of CD4 + peripheral blood T lymphocytes induced by an anti-CD4 monoclonal antibody. Eur J Immunol 18: 333–339, 1988
Carter, W. G., Rauvala, H., and Hakomori, S. I.: Studies on cell adhesion and recognition. II. The kinetics of cell adhesion and cell spreading on surfaces coated with carbohydrate-reactive proteins (glycosidases and lectins) and fibronectin. J Cell Biol 88: 138–148, 1981
Chaudhary, V. K., Mizukami, T., Fuerst, T. R., Fitzgerald, D. J., Moss, B., and Berger, E. A.: Selective killing of HIV-infected cells by recombinant human CD4-Pseudomonas exotoxin hybrid protein. Nature 335: 369–372, 1988
Chuck, R. S., Cantor, C. R., and Tse, D. B.: CD4-T-cell antigen receptor complexes on human leukemia T cells. Proc Natl Acad Sci USA 87: 5021–5025, 1990
Clayton, L. K., Sieh, H., Pious, D. A., and Reinherz, E. L.: Identification of human CD4 residues affecting class II MHC versus HIV gp 120 binding. Nature 339: 548–551, 1989
Cordonnier, A., Montagnier, L., and Emerman, M.: Single amino-acid changes in HIV envelope effect viral tropism and receptor binding. Nature 340: 571–574, 1989
Deen, C. D., McDougal, J. S., Inacker, R., Folena-Wasserman, G., Arthos, J., Rosenberg, J., Maddon, P. J., Axel, R., and Sweet, R.: A soluble form of CD4 (T4) protein inhibits AIDS virus infection. Nature 331: 82–84, 1988
Doyle, C. and Strominger, J. L.: Interaction between CD4 and class II MHC molecules mediates cell adhesion. Nature 330: 256–259, 1987
Gay, D., Maddon, P., Sekaly, R., Talle, M. A., Godfrey, M., Long, E., Goldstein, G., Chess, C., Axel, R., Kappler, J., and Marrack, P.: Functional interaction between human T-cell protein CD4 and the major histocompatibility complex HLA-DR antigen. Nature 328: 626–629, 1987
Golding, H., Robey, F. A., Gates, F. T., Linder, W., Bening, P. R., Hoffman, T., and Golding, B.: Identification of homologous regions in human immunodeficiency virus I gp41 and human class II β1 domain. I. Monoclonal antibodies against the gp41-derived peptide and patients' sera react with native HLA class II antigens, suggesting a role for autoimmunity in the pathogenesis of acquired immune deficiency syndrome. J Exp Med 167: 914–923, 1988
Janeway, C. A.: The role of CD4 in T-cell activation: accessory molecule or co-receptor. Immunol Today 10: 234–238, 1989
Janeway, Jr., C. A., Canding, S., Jones, B., Murray, J., Portoles, P., Rasmussen, R., Rojo, J., Saizawa, K., West, J., and Bottomly, K.: CD4(+) T cells: specificity and function. Immunol Rev 101: 39–80, 1988
Lamarre, D., Ashkenazi, A., Fleury, S., Smith, D. H., Sekaly, R. P., and Capon, D. J.: The MHC-Binding and gp 120-binding functions of CD4 are separable. Science 245: 743–746, 1989a
Lamarre, D., Capon, D. J., Karp, D. R., Gregory, T., Long, E. O., and Sekaly, R. P.: Class II MHC molecules and the HIV gp120 envelope protein interact with functionally distinct regions of the CD4 molecule. EMBO J 8: 3271–3277, 1989b
Lasky, L. A., Nakamura, G., Smith, D. H., Fennie, C., Shimasaki, C., Patzer, E., Berman, P., Gregory, T., and Capon, D. J.: Delineation of a region of the human immunodeficiency virus type 1 gp120 glycoprotein critical for interaction with the CD4 receptor. Cell 50: 975–985, 1987
Lifson, J. E., Hwang, K. M., Nara, P. L., Fraser, B., Padgett, M., Dunlop, N. M., and Eiden, L. E.: Synthetic CD4 peptide derivatives that inhibit HIV infection and cytopathicity. Science 241: 712–716, 1988
Maddon, P. J., Littman, D. R., Godfrey, M., Maddon, D. E., Chess, L., and Axel, R.: The isolation and nucleotide sequence of a cDNA encoding the T cell surface protein T4: a new member of the immunoglobulin gene family. Cell 42: 93–104, 1985
Marrack, P., Endres, R., Schimonkevitz, R., Zlotnik, A., Dialynas, D., Fitch, F., and Kappler, J.: The major histocompatibility complex-restricted antigen receptor on T cells. II. Role of the L3T4 product. J Exp Med 158: 1077–1091, 1983
Mazerolles, F., Durandy, A., Piatier-Tonneau, D., Charron, D., Montagnier, L., Auffray, C., and Fischer, A.: Immunosuppressive properties of synthetic peptides derived from CD4 and HLA-DR antigens. Cell 55: 497–504, 1988
Mazerolles, F., Amblard, F., Lumbroso, C., Van de Moortele, P. F., Lecomte, O., Barbat, C., Piatier-Tonneau, D., Auffray, C., and Fischer, A.: Regulation of T helper-B lymphocyte adhesion through CD4-HLA class II interaction. Eur J Immunol 20: 637–644, 1990
Mittler, R. S., Goldman, S. J., Spitalny, G. L., and Burakoff, S. J.: T-cell receptor-CD4 physical association in a murine T-cell hybridoma: Induction by antigen receptor ligation. Proc Natl Acad Sci USA 86: 8531–8535, 1989
Norment, A. M., Salter, R. D., Parham, P., Engelhard, V. H., and Littman, D. R.: Cell-cell adhesion mediated by CD8 and MHC class I molecules.Nature 336: 79–81, 1988
Parnes, J. R.: Molecular biology and function of CD4 and CD8. Adv Immunol 44: 265–311, 1989
Robey, E. and Axel, R.: CD4: collaborator in immune recognitio and HIV infection. Cell 60: 697–700, 1990
Ryu, S. E., Kwong, P. D., Truneh, A., Porter, T. G., Arthos, J., Rosenberg, M., Dai, X., Xuong, N. H., Axel, R., Sweet, R. W., and Hendrickson, W. A.: Crystal structure of an HIV-binding recombinant fragment of human CD4. Nature 345: 41–46, 1990
Sattentau, Q. J. and Weiss, R. A.: The CD4 antigen: physiological ligand and HIV receptor. Cell 52: 631–633, 1988
Seed, B. and Aruffo, A.: Molecular cloning of the CD2 antigen, the T-cell erythrocyte receptor by a rapid immunoselection procedure. Proc Natl Acad Sci USA 84: 3365–3369, 1987
Till, M. A., Ghetie, V., Gregory, T., Patzer, E. J., Porter, J. P., Uhr, J. W., Capon, D. J., and Vitetta, E. S.: HIV-infected cells are killed by rCD4-Ricin A chain. Science 242: 1166–1168, 1988
Traunecker, A., Schneider, J., Kiefer, H., and Karjalainen, K.: Highly efficient neutralization of HIV with recombinant CD4 immunoglobulin molecules. Nature 339: 68–70, 1989
Turner, J. M., Brodsky, M. H., Irving, B. A., Levin, S. D., Perlmutter, R. M., and Littman, D. R.: Interaction of the unique N-terminal region of tyrosine kinase p56lck with cytoplasmic domains of CD4 and CD8 is mediated by cysteine motifs. Cell 60: 755–765, 1990
Wang, J., Yan, Y., Garett, T. P. J., Liu, J., Rodgers, D. W., Garlick, R. L., Tarr, G. E., Husain, Y., Reinherz, E. L., and Harrison, S. C.: Atomic structure of a fragment human CD4 containing two immunoglobulin-like domains. Nature 348: 411–418, 1990
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Piatier-Tonneau, D., Gastinel, LN., Amblard, F. et al. Interaction of CD4 with HLA class II antigens and HIV gp120. Immunogenetics 34, 121–128 (1991). https://doi.org/10.1007/BF00211424
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DOI: https://doi.org/10.1007/BF00211424