Engagement of class I major histocompatibility complex molecules by cell surface CD8 delivers an activation signal.
Recent evidence has demonstrated that cross-linking class I major histocompatibility complex (MHC) molecules on human T cells with monoclonal antibodies (mAb) triggers T cell activation. The only known natural ligand for MHC class I molecules is CD8. Therefore, the possibility that CD8+ T cells might provide activation signals to other T cells by engaging MHC class I molecules was examined by culturing CD4+ peripheral blood T cells with Chinese hamster ovary cells (CHO) cells that had been transfected with the alpha chain or alpha and beta chains of CD8 and assessing interleukin (IL)-2 production. CD4+ T cells did not secrete IL-2 when cultured alone, with control or CD8+ CHO cells. In contrast, CD4+ T cells produced IL-2 when cultured with CD8+ CHO cells and co-stimulated with phorbol myristate acetate (PMA) or mAb to CD3 or CD28. PMA stimulated substantially less IL-2 when control CHO cells were employed and the mAb to CD3 and CD28 did not stimulate IL-2 production in the presence of control CHO cells. The co-stimulatory activity of CD8+ CHO cells was completely eliminated by mAb to CD8 or MHC class I molecules. The data demonstrate that CD8 can interact with MHC class I molecules expressed on T cells and deliver a costimulatory signal that increases IL-2 production. Thus, engagement of MHC class I molecules by its natural ligand, CD8, provides an activation signal to T cells. Under some circumstances, such interactions may amplify the responses of T cells.
Geppert
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Harold C. Simmons Arthritis Research Center, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas 75235.
Nguyen
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Lipsky
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D000818:Animals; D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D018106:CD28 Antigens; D017252:CD3 Complex; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016827:CD8 Antigens / Q000276:immunology*; D002478:Cells, Cultured; D006168:Guinea Pigs; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D014162:Transfection
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018106:CD28 Antigens; D017252:CD3 Complex; D016827:CD8 Antigens; D015395:Histocompatibility Antigens Class I; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell