The role of the CD28 receptor during T cell responses to antigen.
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.
Linsley
P S
PS
Department of Cellular Immunology, Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle, Washington 98121.
Ledbetter
J A
JA
D000069594:Abatacept; D000818:Animals; D000941:Antigens; D015703:Antigens, CD / Q000235:genetics; D000943:Antigens, Differentiation / Q000235:genetics; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics; D001402:B-Lymphocytes / Q000276:immunology; D018106:CD28 Antigens; D060908:CTLA-4 Antigen; D006801:Humans; D007108:Immune Tolerance; D018796:Immunoconjugates; D011971:Receptors, Immunologic / Q000235:genetics; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D000941:Antigens; D015703:Antigens, CD; D000943:Antigens, Differentiation; D000945:Antigens, Differentiation, T-Lymphocyte; D018106:CD28 Antigens; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D018796:Immunoconjugates; D011971:Receptors, Immunologic; D000069594:Abatacept