Skip to main content
NCBI home page
Immunology logoLink to Immunology
. 1991 Oct;74(2):191–196.

Conservation of a polyanion binding site in mammalian and avian CD4.

C R Parish 1, H S Warren 1
PMCID: PMC1384592  PMID: 1748468

Abstract

A polyanion binding site was identified recently on human CD4 which is distinct from the human immunodeficiency virus (HIV)-gp120 binding region but which incorporates the first two immunoglobulin (Ig)-like domains of the molecule. To determine if this site is conserved in other species, several polyanions that blocked monoclonal antibody (mAb) binding to human CD4 were examined for their ability to inhibit the binding of mAb to mouse, rat, pig, sheep and chicken CD4. It was found that aurintricarboxylic acid (ATA) was a particularly effective inhibitor, blocking mAb binding to human, mouse, pig, sheep and rat CD4 by greater than 90% and to chicken CD4 by 80-90%. The polyanions dextran sulphate (DxS), polyvinyl sulphate (PVS) and polyanethole sulphonate (PAS) were also effective inhibitors of anti-CD4 mAb binding in most species, although there were clear species differences in the effects obtained. The polyanions did not inhibit mAb binding to a variety of other cell-surface antigens in the different species, with the exception of sheep CD8, suggesting that the inhibitory effects observed were essentially CD4 specific. Collectively these data indicate that a polyanion binding site is conserved in mammalian and avian CD4. Comparison of the amino acid sequences of human, mouse and rat CD4 revealed that basic residues in human CD4 which could participate in a polyanion binding site are conserved in mouse and rat CD4. It is proposed that this conserved polyanion binding site of CD4 interacts with a sulphated glycosaminoglycan chain which is associated with class II major histocompatibility complex (MHC) molecules containing recently processed antigen.

Full text

PDF
191

Selected References

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

  1. Arthos J., Deen K. C., Chaikin M. A., Fornwald J. A., Sathe G., Sattentau Q. J., Clapham P. R., Weiss R. A., McDougal J. S., Pietropaolo C. Identification of the residues in human CD4 critical for the binding of HIV. Cell. 1989 May 5;57(3):469–481. doi: 10.1016/0092-8674(89)90922-7. [DOI] [PubMed] [Google Scholar]
  2. Baba M., Pauwels R., Balzarini J., Arnout J., Desmyter J., De Clercq E. Mechanism of inhibitory effect of dextran sulfate and heparin on replication of human immunodeficiency virus in vitro. Proc Natl Acad Sci U S A. 1988 Aug;85(16):6132–6136. doi: 10.1073/pnas.85.16.6132. [DOI] [PMC free article] [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. Clark S. J., Jefferies W. A., Barclay A. N., Gagnon J., Williams A. F. 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 U S A. 1987 Mar;84(6):1649–1653. doi: 10.1073/pnas.84.6.1649. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Clayton L. K., Hussey R. E., Steinbrich R., Ramachandran H., Husain Y., Reinherz E. L. Substitution of murine for human CD4 residues identifies amino acids critical for HIV-gp120 binding. Nature. 1988 Sep 22;335(6188):363–366. doi: 10.1038/335363a0. [DOI] [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. Doyle C., Strominger J. L. Interaction between CD4 and class II MHC molecules mediates cell adhesion. Nature. 1987 Nov 19;330(6145):256–259. doi: 10.1038/330256a0. [DOI] [PubMed] [Google Scholar]
  9. Jameson B. A., Rao P. E., Kong L. I., Hahn B. H., Shaw G. M., Hood L. E., Kent S. B. Location and chemical synthesis of a binding site for HIV-1 on the CD4 protein. Science. 1988 Jun 3;240(4857):1335–1339. doi: 10.1126/science.2453925. [DOI] [PubMed] [Google Scholar]
  10. 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]
  11. Krensky A. M., Reiss C. S., Mier J. W., Strominger J. L., Burakoff S. J. Long-term human cytolytic T-cell lines allospecific for HLA-DR6 antigen are OKT4+. Proc Natl Acad Sci U S A. 1982 Apr;79(7):2365–2369. doi: 10.1073/pnas.79.7.2365. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Lederman S., Gulick R., Chess L. Dextran sulfate and heparin interact with CD4 molecules to inhibit the binding of coat protein (gp120) of HIV. J Immunol. 1989 Aug 15;143(4):1149–1154. [PubMed] [Google Scholar]
  13. Littman D. R., Gettner S. N. Unusual intron in the immunoglobulin domain of the newly isolated murine CD4 (L3T4) gene. 1987 Jan 29-Feb 4Nature. 325(6103):453–455. doi: 10.1038/325453a0. [DOI] [PubMed] [Google Scholar]
  14. 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]
  15. Meuer S. C., Schlossman S. F., Reinherz E. L. Clonal analysis of human cytotoxic T lymphocytes: T4+ and T8+ effector T cells recognize products of different major histocompatibility complex regions. Proc Natl Acad Sci U S A. 1982 Jul;79(14):4395–4399. doi: 10.1073/pnas.79.14.4395. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Miller J., Hatch J. A., Simonis S., Cullen S. E. Identification of the glycosaminoglycan-attachment site of mouse invariant-chain proteoglycan core protein by site-directed mutagenesis. Proc Natl Acad Sci U S A. 1988 Mar;85(5):1359–1363. doi: 10.1073/pnas.85.5.1359. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Mitsuya H., Looney D. J., Kuno S., Ueno R., Wong-Staal F., Broder S. Dextran sulfate suppression of viruses in the HIV family: inhibition of virion binding to CD4+ cells. Science. 1988 Apr 29;240(4852):646–649. doi: 10.1126/science.2452480. [DOI] [PubMed] [Google Scholar]
  18. Mizukami T., Fuerst T. R., Berger E. A., Moss B. Binding region for human immunodeficiency virus (HIV) and epitopes for HIV-blocking monoclonal antibodies of the CD4 molecule defined by site-directed mutagenesis. Proc Natl Acad Sci U S A. 1988 Dec;85(23):9273–9277. doi: 10.1073/pnas.85.23.9273. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Parish C. R., Low L., Warren H. S., Cunningham A. L. A polyanion binding site on the CD4 molecule. Proximity to the HIV-gp120 binding region. J Immunol. 1990 Aug 15;145(4):1188–1195. [PubMed] [Google Scholar]
  20. Parish C. R., McPhun V., Warren H. S. Is a natural ligand of the T lymphocyte CD2 molecule a sulfated carbohydrate? J Immunol. 1988 Nov 15;141(10):3498–3504. [PubMed] [Google Scholar]
  21. Parnes J. R. Molecular biology and function of CD4 and CD8. Adv Immunol. 1989;44:265–311. doi: 10.1016/s0065-2776(08)60644-6. [DOI] [PubMed] [Google Scholar]
  22. Peterson C. B., Noyes C. M., Pecon J. M., Church F. C., Blackburn M. N. Identification of a lysyl residue in antithrombin which is essential for heparin binding. J Biol Chem. 1987 Jun 15;262(17):8061–8065. [PubMed] [Google Scholar]
  23. Pierres A., Naquet P., Van Agthoven A., Bekkhoucha F., Denizot F., Mishal Z., Schmitt-Verhulst A. M., Pierres M. A rat anti-mouse T4 monoclonal antibody (H129.19) inhibits the proliferation of Ia-reactive T cell clones and delineates two phenotypically distinct (T4+, Lyt-2,3-, and T4-, Lyt-2,3+) subsets among anti-Ia cytolytic T cell clones. J Immunol. 1984 Jun;132(6):2775–2782. [PubMed] [Google Scholar]
  24. Richardson N. E., Brown N. R., Hussey R. E., Vaid A., Matthews T. J., Bolognesi D. P., Reinherz E. L. Binding site for human immunodeficiency virus coat protein gp120 is located in the NH2-terminal region of T4 (CD4) and requires the intact variable-region-like domain. Proc Natl Acad Sci U S A. 1988 Aug;85(16):6102–6106. doi: 10.1073/pnas.85.16.6102. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Robey E., Axel R. CD4: collaborator in immune recognition and HIV infection. Cell. 1990 Mar 9;60(5):697–700. doi: 10.1016/0092-8674(90)90082-p. [DOI] [PubMed] [Google Scholar]
  26. Rosamond S., Brown L., Gomez C., Braciale T. J., Schwartz B. D. Xyloside inhibits synthesis of the class II-associated chondroitin sulfate proteoglycan and antigen presentation events. J Immunol. 1987 Sep 15;139(6):1946–1951. [PubMed] [Google Scholar]
  27. Sant A. J., Cullen S. E., Giacoletto K. S., Schwartz B. D. Invariant chain is the core protein of the Ia-associated chondroitin sulfate proteoglycan. J Exp Med. 1985 Dec 1;162(6):1916–1934. doi: 10.1084/jem.162.6.1916. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Sant A. J., Cullen S. E., Schwartz B. D. Biosynthetic relationships of the chondroitin sulfate proteoglycan with Ia and invariant chain glycoproteins. J Immunol. 1985 Jul;135(1):416–422. [PubMed] [Google Scholar]
  29. Sant A. J., Cullen S. E., Schwartz B. D. Identification of a sulfate-bearing molecule associated with HLA class II antigens. Proc Natl Acad Sci U S A. 1984 Mar;81(5):1534–1538. doi: 10.1073/pnas.81.5.1534. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Sant A. J., Schwartz B. D., Cullen S. E. Identification of a new component in the murine Ia molecular complex. J Exp Med. 1983 Dec 1;158(6):1979–1992. doi: 10.1084/jem.158.6.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Sattentau Q. J., Arthos J., Deen K., Hanna N., Healey D., Beverley P. C., Sweet R., Truneh A. Structural analysis of the human immunodeficiency virus-binding domain of CD4. Epitope mapping with site-directed mutants and anti-idiotypes. J Exp Med. 1989 Oct 1;170(4):1319–1334. doi: 10.1084/jem.170.4.1319. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Schols D., Baba M., Pauwels R., Desmyter J., De Clercq E. Specific interaction of aurintricarboxylic acid with the human immunodeficiency virus/CD4 cell receptor. Proc Natl Acad Sci U S A. 1989 May;86(9):3322–3326. doi: 10.1073/pnas.86.9.3322. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Sivak L. E., Harris M. R., Kindle C., Cullen S. E. Inhibition of proteoglycan synthesis eliminates the proteoglycan form of Ia-associated invariant chain and depresses antigen presentation. J Immunol. 1987 Mar 1;138(5):1319–1321. [PubMed] [Google Scholar]
  34. St Charles R., Walz D. A., Edwards B. F. The three-dimensional structure of bovine platelet factor 4 at 3.0-A resolution. J Biol Chem. 1989 Feb 5;264(4):2092–2099. [PubMed] [Google Scholar]
  35. Thiele B., Braig H. R., Ehm I., Kunze R., Ruf B. Influence of sulfated carbohydrates on the accessibility of CD4 and other CD molecules on the cell surface and implications for human immunodeficiency virus infection. Eur J Immunol. 1989 Jun;19(6):1161–1164. doi: 10.1002/eji.1830190630. [DOI] [PubMed] [Google Scholar]
  36. Tourvieille B., Gorman S. D., Field E. H., Hunkapiller T., Parnes J. R. Isolation and sequence of L3T4 complementary DNA clones: expression in T cells and brain. Science. 1986 Oct 31;234(4776):610–614. doi: 10.1126/science.3094146. [DOI] [PubMed] [Google Scholar]
  37. Warren H. S., Parish C. R. Mapping the dextran sulfate binding site on CD2. Immunol Cell Biol. 1990 Jun;68(Pt 3):199–205. doi: 10.1038/icb.1990.28. [DOI] [PubMed] [Google Scholar]

Articles from Immunology are provided here courtesy of British Society for Immunology

RESOURCES