The role of the CD28 receptor during T cell responses to antigen

Annu Rev Immunol. 1993;11:191-212. doi: 10.1146/annurev.iy.11.040193.001203.


The CD28 receptor is stimulated during the contact of T cells with antigen-presenting cells. A counter-receptor for CD28 is the B7 molecule expressed on activated B cells, dendritic cells, and macrophages. B7 also binds to CTLA-4, a receptor that is structurally related to CD28. CTLA-4 is expressed in low copy number by T cells only after activation, but it binds B7 with approximately 20-fold higher affinity than CD28. Inhibition of B7-CD28 interactions blocks immune responses in vitro and in vivo. Therefore, CD28 receptor stimulation is required for T cell responses to antigens and for B cell responses to T-dependent antigens. During T cell responses to antigens, CD28 receptor stimulation may be required to prevent clonal inactivation or anergy. CD28 receptor ligation induces tyrosine phosphorylation of specific substrates, including phospholipase C gamma 1, and triggers both calcium-dependent and calcium-independent signals. The CD28 costimulatory receptor represents a novel target for immunosuppressive drugs.

Publication types

  • Review

MeSH terms

  • Abatacept
  • Animals
  • Antigens
  • Antigens, CD* / genetics
  • Antigens, Differentiation / genetics
  • Antigens, Differentiation, T-Lymphocyte* / genetics
  • B-Lymphocytes / immunology
  • CD28 Antigens
  • CTLA-4 Antigen
  • Humans
  • Immune Tolerance
  • Immunoconjugates*
  • Receptors, Immunologic* / genetics
  • Signal Transduction / immunology
  • T-Lymphocytes / immunology*


  • Antigens
  • Antigens, CD
  • Antigens, Differentiation
  • Antigens, Differentiation, T-Lymphocyte
  • CD28 Antigens
  • CTLA-4 Antigen
  • CTLA4 protein, human
  • Immunoconjugates
  • Receptors, Immunologic
  • Abatacept