Skip to main content
NCBI home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1991 Jul 1;174(1):53–62. doi: 10.1084/jem.174.1.53

Human immunodeficiency virus type 1 gp120 mimics a hidden monomorphic epitope borne by class I major histocompatibility complex heavy chains

PMCID: PMC2118897  PMID: 1711567

Abstract

Murine monoclonal antibodies (mAbs) M38 and L31 define two epitopes of a surface protein of activated lymphocytes and monocytes. It has been shown that M38 also defines a crossreactive epitope of human immunodeficiency virus type 1 (HIV-1) gp120 (Beretta et al., 1987. Eur. J. Immunol. 17: 1793). The mAb inhibits syncytia formation driven by HIV-1-infected cells. The surface protein was demonstrated to be a class I MHC alpha chain, by sequence analysis of the corresponding cDNA and by immunological means. The epitopes defined by mAbs M38 and L31 are monomorphic and hidden (i.e., inaccessible to antibodies) on native HLA molecules expressed by resting cells, but can be evidenced on denatured proteins by Western blot analysis. The two epitopes become accessible after activation processes have been implemented, likely reflecting a conformational alteration of alpha chains (such as that described by Schnabl et al. 1990. J. Exp. Med. 171:1431). Consistent with molecular data are the results of functional analysis, which indicate that the molecule recognized by M38 and L31 is a gate for pleiotropic negative signals, since the two mAbs were shown to inhibit monocyte antigen presentation and lymphocyte mitogenic proliferation, respectively.

Full Text

The Full Text of this article is available as a PDF (1.1 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Beretta A., Grassi F., Pelagi M., Clivio A., Parravicini C., Giovinazzo G., Andronico F., Lopalco L., Verani P., Buttò S. HIV env glycoprotein shares a cross-reacting epitope with a surface protein present on activated human monocytes and involved in antigen presentation. Eur J Immunol. 1987 Dec;17(12):1793–1798. doi: 10.1002/eji.1830171218. [DOI] [PubMed] [Google Scholar]
  2. Beverley P. C., Callard R. E. Distinctive functional characteristics of human "T" lymphocytes defined by E rosetting or a monoclonal anti-T cell antibody. Eur J Immunol. 1981 Apr;11(4):329–334. doi: 10.1002/eji.1830110412. [DOI] [PubMed] [Google Scholar]
  3. Biddison W. E., Rao P. E., Talle M. A., Goldstein G., Shaw S. Possible involvement of the OKT4 molecule in T cell recognition of class II HLA antigens. Evidence from studies of cytotoxic T lymphocytes specific for SB antigens. J Exp Med. 1982 Oct 1;156(4):1065–1076. doi: 10.1084/jem.156.4.1065. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Chanh T. C., Dreesman G. R., Kennedy R. C. Monoclonal anti-idiotypic antibody mimics the CD4 receptor and binds human immunodeficiency virus. Proc Natl Acad Sci U S A. 1987 Jun;84(11):3891–3895. doi: 10.1073/pnas.84.11.3891. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Chouaib S., Welte K., Dupont B. Differential effect of anti-beta 2-microglobulin on IL 2 production and IL 2 receptor expression in the primary mixed lymphocyte culture reaction. J Immunol. 1985 Feb;134(2):940–948. [PubMed] [Google Scholar]
  6. Clayton L. K., Sieh M., Pious D. A., Reinherz E. L. Identification of human CD4 residues affecting class II MHC versus HIV-1 gp120 binding. Nature. 1989 Jun 15;339(6225):548–551. doi: 10.1038/339548a0. [DOI] [PubMed] [Google Scholar]
  7. Dalgleish A. G., Beverley P. C., Clapham P. R., Crawford D. H., Greaves M. F., Weiss R. A. The CD4 (T4) antigen is an essential component of the receptor for the AIDS retrovirus. Nature. 1984 Dec 20;312(5996):763–767. doi: 10.1038/312763a0. [DOI] [PubMed] [Google Scholar]
  8. Folks T. M., Powell D., Lightfoote M., Koenig S., Fauci A. S., Benn S., Rabson A., Daugherty D., Gendelman H. E., Hoggan M. D. Biological and biochemical characterization of a cloned Leu-3- cell surviving infection with the acquired immune deficiency syndrome retrovirus. J Exp Med. 1986 Jul 1;164(1):280–290. doi: 10.1084/jem.164.1.280. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Friedrich B., Lundström M., Gullberg M. Interleukin-2 versus phorbol-ester-induced cellular events in normal T-lymphocytes. Med Oncol Tumor Pharmacother. 1986;3(3-4):237–246. doi: 10.1007/BF02935000. [DOI] [PubMed] [Google Scholar]
  10. Gay D., Maddon P., Sekaly R., Talle M. A., Godfrey M., Long E., Goldstein G., Chess L., Axel R., Kappler J. Functional interaction between human T-cell protein CD4 and the major histocompatibility complex HLA-DR antigen. Nature. 1987 Aug 13;328(6131):626–629. doi: 10.1038/328626a0. [DOI] [PubMed] [Google Scholar]
  11. Gelderblom H. R., Ozel M., Pauli G. Morphogenesis and morphology of HIV. Structure-function relations. Arch Virol. 1989;106(1-2):1–13. doi: 10.1007/BF01311033. [DOI] [PubMed] [Google Scholar]
  12. Gillis S., Ferm M. M., Ou W., Smith K. A. T cell growth factor: parameters of production and a quantitative microassay for activity. J Immunol. 1978 Jun;120(6):2027–2032. [PubMed] [Google Scholar]
  13. Golding H., Robey F. A., Gates F. T., 3rd, Linder W., Beining P. R., Hoffman T., Golding B. Identification of homologous regions in human immunodeficiency virus I gp41 and human MHC class II beta 1 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. 1988 Mar 1;167(3):914–923. doi: 10.1084/jem.167.3.914. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Klatzmann D., Champagne E., Chamaret S., Gruest J., Guetard D., Hercend T., Gluckman J. C., Montagnier L. T-lymphocyte T4 molecule behaves as the receptor for human retrovirus LAV. Nature. 1984 Dec 20;312(5996):767–768. doi: 10.1038/312767a0. [DOI] [PubMed] [Google Scholar]
  15. Kruisbeek A. M., Mond J. J., Fowlkes B. J., Carmen J. A., Bridges S., Longo D. L. Absence of the Lyt-2-,L3T4+ lineage of T cells in mice treated neonatally with anti-I-A correlates with absence of intrathymic I-A-bearing antigen-presenting cell function. J Exp Med. 1985 May 1;161(5):1029–1047. doi: 10.1084/jem.161.5.1029. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Kupfer A., Singer S. J., Janeway C. A., Jr, Swain S. L. Coclustering of CD4 (L3T4) molecule with the T-cell receptor is induced by specific direct interaction of helper T cells and antigen-presenting cells. Proc Natl Acad Sci U S A. 1987 Aug;84(16):5888–5892. doi: 10.1073/pnas.84.16.5888. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Lamarre D., Ashkenazi A., Fleury S., Smith D. H., Sekaly R. P., Capon D. J. The MHC-binding and gp120-binding functions of CD4 are separable. Science. 1989 Aug 18;245(4919):743–746. doi: 10.1126/science.2549633. [DOI] [PubMed] [Google Scholar]
  18. Lanzavecchia A., Roosnek E., Gregory T., Berman P., Abrignani S. T cells can present antigens such as HIV gp120 targeted to their own surface molecules. Nature. 1988 Aug 11;334(6182):530–532. doi: 10.1038/334530a0. [DOI] [PubMed] [Google Scholar]
  19. Marrack P., Endres R., Shimonkevitz R., Zlotnik A., Dialynas D., Fitch F., Kappler J. The major histocompatibility complex-restricted antigen receptor on T cells. II. Role of the L3T4 product. J Exp Med. 1983 Oct 1;158(4):1077–1091. doi: 10.1084/jem.158.4.1077. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. McDougal J. S., Kennedy M. S., Sligh J. M., Cort S. P., Mawle A., Nicholson J. K. Binding of HTLV-III/LAV to T4+ T cells by a complex of the 110K viral protein and the T4 molecule. Science. 1986 Jan 24;231(4736):382–385. doi: 10.1126/science.3001934. [DOI] [PubMed] [Google Scholar]
  21. Mittler R. S., Hoffmann M. K. Synergism between HIV gp120 and gp120-specific antibody in blocking human T cell activation. Science. 1989 Sep 22;245(4924):1380–1382. doi: 10.1126/science.2571187. [DOI] [PubMed] [Google Scholar]
  22. Russo C., Ng A. K., Pellegrino M. A., Ferrone S. The monoclonal antibody CR11-351 discriminates HLA-A2 variants identified by T cells. Immunogenetics. 1983;18(1):23–35. doi: 10.1007/BF00401353. [DOI] [PubMed] [Google Scholar]
  23. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Schnabl E., Stockinger H., Majdic O., Gaugitsch H., Lindley I. J., Maurer D., Hajek-Rosenmayr A., Knapp W. Activated human T lymphocytes express MHC class I heavy chains not associated with beta 2-microglobulin. J Exp Med. 1990 May 1;171(5):1431–1442. doi: 10.1084/jem.171.5.1431. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Siliciano R. F., Lawton T., Knall C., Karr R. W., Berman P., Gregory T., Reinherz E. L. Analysis of host-virus interactions in AIDS with anti-gp120 T cell clones: effect of HIV sequence variation and a mechanism for CD4+ cell depletion. Cell. 1988 Aug 12;54(4):561–575. doi: 10.1016/0092-8674(88)90078-5. [DOI] [PubMed] [Google Scholar]
  26. Sleckman B. P., Peterson A., Jones W. K., Foran J. A., Greenstein J. L., Seed B., Burakoff S. J. Expression and function of CD4 in a murine T-cell hybridoma. Nature. 1987 Jul 23;328(6128):351–353. doi: 10.1038/328351a0. [DOI] [PubMed] [Google Scholar]
  27. Smith K. A., Favata M. F., Oroszlan S. Production and characterization of monoclonal antibodies to human interleukin 2: strategy and tactics. J Immunol. 1983 Oct;131(4):1808–1815. [PubMed] [Google Scholar]
  28. Smith M. H., Barber B. H. The conformational flexibility of class I H-2 molecules as revealed by anti-peptide antibodies specific for intracytoplasmic determinants: differential reactivity of beta 2-microglobulin "bound" and "free" H-2Kb heavy chains. Mol Immunol. 1990 Feb;27(2):169–180. doi: 10.1016/0161-5890(90)90112-d. [DOI] [PubMed] [Google Scholar]
  29. Snary D., Goodfellow P., Bodmer W. F., Crumpton M. J. Evidence against a dimeric structure for membrane-bound HLA antigens. Nature. 1975 Nov 20;258(5532):240–242. doi: 10.1038/258240a0. [DOI] [PubMed] [Google Scholar]
  30. Spagnoli G. C., Ausiello C. M., Cassone A., Casciani C. U., Bellone G., Malavasi F. Inhibitory effects of anti-HLA-A, B, C heavy chain and anti-beta 2 microglobulin monoclonal antibodies on alloantigen and microbial antigen-induced immune responses in vitro. Scand J Immunol. 1987 Jun;25(6):555–565. doi: 10.1111/j.1365-3083.1987.tb01081.x. [DOI] [PubMed] [Google Scholar]
  31. Sterkers G., Henin Y., Kalil J., Bagot M., Levy J. P. Influence of HLA class I- and class II-specific monoclonal antibodies on DR-restricted lymphoproliferative responses. I. Unseparated populations of effector cells. J Immunol. 1983 Dec;131(6):2735–2740. [PubMed] [Google Scholar]
  32. Takiguchi M., Nishimura I., Hayashi H., Karakl S., Kariyone A., Kano K. The structure and expression of genes encoding serologically undetected HLA-C locus antigens. J Immunol. 1989 Aug 15;143(4):1372–1378. [PubMed] [Google Scholar]
  33. Tibensky D., DeMars R., Holowachuk E. W., Delovitch T. L. Sequence and gene transfer analyses of HLA-CwBL18 (HLA-C blank) and HLA-Cw5 genes. Implications for the control of expression and immunogenicity of HLA-C antigens. J Immunol. 1989 Jul 1;143(1):348–355. [PubMed] [Google Scholar]
  34. Turco M. C., De Felice M., Corbo L., Morrone G., Mertelsmann R., Ferrone S., Venuta S. Regulatory role of a monomorphic determinant of HLA Class I antigens in T cell proliferation. J Immunol. 1985 Oct;135(4):2268–2273. [PubMed] [Google Scholar]
  35. Young R. A., Davis R. W. Efficient isolation of genes by using antibody probes. Proc Natl Acad Sci U S A. 1983 Mar;80(5):1194–1198. doi: 10.1073/pnas.80.5.1194. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES