Skip to main content
PMC home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1991 Mar 1;173(3):721–730. doi: 10.1084/jem.173.3.721

Binding of the B cell activation antigen B7 to CD28 costimulates T cell proliferation and interleukin 2 mRNA accumulation

PMCID: PMC2118836  PMID: 1847722

Abstract

A successful immune response requires intercellular contact between T and B lymphocytes. We recently showed that CD28, a T cell surface protein that regulates an activation pathway, could mediate intercellular adhesion with activated B cells by interaction with the B7 antigen. Here we show that CD28 is the primary receptor for B7 on activated peripheral blood T cells, that CD28 binds to B7 in the absence of other accessory molecules, and that interaction between CD28 and B7 is costimulatory for T cell activation. To characterize the binding of CD28 to B7, we have produced genetic fusions of the extracellular portions of B7 and CD28, and immunoglobulin (Ig) C gamma 1 chains. 125I-labeled B7 Ig bound to CD28-transfected Chinese hamster ovary (CHO) cells, and to immobilized CD28 Ig with a Kd approximately 200 nM. B7 Ig also inhibited CD28-mediated cellular adhesion. The function of CD28-B7 interactions during T cell activation was investigated with soluble fusion proteins and with B7-transfected CHO cells. Immobilized B7 Ig and B7+ CHO cells costimulated T cell proliferation. Stimulation of T cells with B7+ CHO cells also specifically increased levels of interleukin 2 transcripts. These results demonstrate that the CD28 signaling pathway could be activated by B7, resulting in increased T cell cytokine production and T cell proliferation. Cellular interactions mediated by B7 and CD28 may represent an important component of the functional interactions between T and B lymphoid cells.

Full Text

The Full Text of this article is available as a PDF (1.2 MB).

Selected References

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

  1. Alzari P. M., Lascombe M. B., Poljak R. J. Three-dimensional structure of antibodies. Annu Rev Immunol. 1988;6:555–580. doi: 10.1146/annurev.iy.06.040188.003011. [DOI] [PubMed] [Google Scholar]
  2. Aruffo A., Seed B. Molecular cloning of a CD28 cDNA by a high-efficiency COS cell expression system. Proc Natl Acad Sci U S A. 1987 Dec;84(23):8573–8577. doi: 10.1073/pnas.84.23.8573. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Aruffo A., Stamenkovic I., Melnick M., Underhill C. B., Seed B. CD44 is the principal cell surface receptor for hyaluronate. Cell. 1990 Jun 29;61(7):1303–1313. doi: 10.1016/0092-8674(90)90694-a. [DOI] [PubMed] [Google Scholar]
  4. Capon D. J., Chamow S. M., Mordenti J., Marsters S. A., Gregory T., Mitsuya H., Byrn R. A., Lucas C., Wurm F. M., Groopman J. E. Designing CD4 immunoadhesins for AIDS therapy. Nature. 1989 Feb 9;337(6207):525–531. doi: 10.1038/337525a0. [DOI] [PubMed] [Google Scholar]
  5. Caput D., Beutler B., Hartog K., Thayer R., Brown-Shimer S., Cerami A. Identification of a common nucleotide sequence in the 3'-untranslated region of mRNA molecules specifying inflammatory mediators. Proc Natl Acad Sci U S A. 1986 Mar;83(6):1670–1674. doi: 10.1073/pnas.83.6.1670. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
  7. 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]
  8. Clevers H., Alarcon B., Wileman T., Terhorst C. The T cell receptor/CD3 complex: a dynamic protein ensemble. Annu Rev Immunol. 1988;6:629–662. doi: 10.1146/annurev.iy.06.040188.003213. [DOI] [PubMed] [Google Scholar]
  9. Damle N. K., Hansen J. A., Good R. A., Gupta S. Monoclonal antibody analysis of human T lymphocyte subpopulations exhibiting autologous mixed lymphocyte reaction. Proc Natl Acad Sci U S A. 1981 Aug;78(8):5096–5098. doi: 10.1073/pnas.78.8.5096. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Dinarello C. A., Mier J. W. Lymphokines. N Engl J Med. 1987 Oct 8;317(15):940–945. doi: 10.1056/NEJM198710083171506. [DOI] [PubMed] [Google Scholar]
  11. Freeman G. J., Freedman A. S., Segil J. M., Lee G., Whitman J. F., Nadler L. M. B7, a new member of the Ig superfamily with unique expression on activated and neoplastic B cells. J Immunol. 1989 Oct 15;143(8):2714–2722. [PubMed] [Google Scholar]
  12. June C. H., Ledbetter J. A., Linsley P. S., Thompson C. B. Role of the CD28 receptor in T-cell activation. Immunol Today. 1990 Jun;11(6):211–216. doi: 10.1016/0167-5699(90)90085-n. [DOI] [PubMed] [Google Scholar]
  13. Lasky L. A., Nakamura G., Smith D. H., Fennie C., Shimasaki C., Patzer E., Berman P., Gregory T., Capon D. J. Delineation of a region of the human immunodeficiency virus type 1 gp120 glycoprotein critical for interaction with the CD4 receptor. Cell. 1987 Sep 11;50(6):975–985. doi: 10.1016/0092-8674(87)90524-1. [DOI] [PubMed] [Google Scholar]
  14. Ledbetter J. A., Imboden J. B., Schieven G. L., Grosmaire L. S., Rabinovitch P. S., Lindsten T., Thompson C. B., June C. H. CD28 ligation in T-cell activation: evidence for two signal transduction pathways. Blood. 1990 Apr 1;75(7):1531–1539. [PubMed] [Google Scholar]
  15. Lesslauer W., Koning F., Ottenhoff T., Giphart M., Goulmy E., van Rood J. J. T90/44 (9.3 antigen). A cell surface molecule with a function in human T cell activation. Eur J Immunol. 1986 Oct;16(10):1289–1296. doi: 10.1002/eji.1830161017. [DOI] [PubMed] [Google Scholar]
  16. Lindstein T., June C. H., Ledbetter J. A., Stella G., Thompson C. B. Regulation of lymphokine messenger RNA stability by a surface-mediated T cell activation pathway. Science. 1989 Apr 21;244(4902):339–343. doi: 10.1126/science.2540528. [DOI] [PubMed] [Google Scholar]
  17. Malik N., Kallestad J. C., Gunderson N. L., Austin S. D., Neubauer M. G., Ochs V., Marquardt H., Zarling J. M., Shoyab M., Wei C. M. Molecular cloning, sequence analysis, and functional expression of a novel growth regulator, oncostatin M. Mol Cell Biol. 1989 Jul;9(7):2847–2853. doi: 10.1128/mcb.9.7.2847. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Matsuyama T., Yamada A., Kay J., Yamada K. M., Akiyama S. K., Schlossman S. F., Morimoto C. Activation of CD4 cells by fibronectin and anti-CD3 antibody. A synergistic effect mediated by the VLA-5 fibronectin receptor complex. J Exp Med. 1989 Oct 1;170(4):1133–1148. doi: 10.1084/jem.170.4.1133. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. 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]
  20. Schwartz R. H. A cell culture model for T lymphocyte clonal anergy. Science. 1990 Jun 15;248(4961):1349–1356. doi: 10.1126/science.2113314. [DOI] [PubMed] [Google Scholar]
  21. 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]
  22. Shaw G., Kamen R. A conserved AU sequence from the 3' untranslated region of GM-CSF mRNA mediates selective mRNA degradation. Cell. 1986 Aug 29;46(5):659–667. doi: 10.1016/0092-8674(86)90341-7. [DOI] [PubMed] [Google Scholar]
  23. Stoolman L. M. Adhesion molecules controlling lymphocyte migration. Cell. 1989 Mar 24;56(6):907–910. doi: 10.1016/0092-8674(89)90620-x. [DOI] [PubMed] [Google Scholar]
  24. Thompson C. B., Lindsten T., Ledbetter J. A., Kunkel S. L., Young H. A., Emerson S. G., Leiden J. M., June C. H. CD28 activation pathway regulates the production of multiple T-cell-derived lymphokines/cytokines. Proc Natl Acad Sci U S A. 1989 Feb;86(4):1333–1337. doi: 10.1073/pnas.86.4.1333. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Vitetta E. S., Baur S., Uhr J. W. Cell surface immunoglobulin. II. Isolation and characterization of immunoglobulin from mouse splenic lymphocytes. J Exp Med. 1971 Jul 1;134(1):242–264. doi: 10.1084/jem.134.1.242. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Webb D. S., Shimizu Y., Van Seventer G. A., Shaw S., Gerrard T. L. LFA-3, CD44, and CD45: physiologic triggers of human monocyte TNF and IL-1 release. Science. 1990 Sep 14;249(4974):1295–1297. doi: 10.1126/science.1697984. [DOI] [PubMed] [Google Scholar]
  27. Weiss A. Structure and function of the T cell antigen receptor. J Clin Invest. 1990 Oct;86(4):1015–1022. doi: 10.1172/JCI114803. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Yokochi T., Holly R. D., Clark E. A. B lymphoblast antigen (BB-1) expressed on Epstein-Barr virus-activated B cell blasts, B lymphoblastoid cell lines, and Burkitt's lymphomas. J Immunol. 1982 Feb;128(2):823–827. [PubMed] [Google Scholar]

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

RESOURCES