Selective signal transduction through the CD3 or CD2 complex is required for class II MHC expression by human T cells.
Ag-dependent activation of human T cells results in high level expression of class II MHC molecules. As part of this process, Ag recognition by TCR generates a series of second signals including protein kinase C, tyrosine kinase, and Ca2+ mobilization. To investigate the role of these second messengers in class II MHC expression, purified T cells were first stimulated by PMA, ionomycin, OKT3 accompanied by IL-2, or the mitogenic anti-CD2 antibodies T112 and T113 and were then stained with FITC-conjugated anti-class I and -class II MHC antibodies for analysis by flow cytometry. OKT3 and IL-2 induced optimal expression of HLA-DR (DR) on 70% of T cells with high density. Despite their high mitogenicity, induction of class II MHC expression by PMA, even with co-stimulation by ionomycin, was reduced to less than 20% of T cells, with an intensity 50-fold lower than in OKT3/IL-2-stimulated T cells. Furthermore, PMA inhibited class II MHC expression by OKT3/IL-2-stimulated T cells in a dose-dependent manner and additional stimuli, such as IL-1, IL-4, IFN-gamma, TCR cross-linkers, or monocytes, did not restore class II MHC expression by PMA-activated T cells. DR beta mRNA analysis showed that the low induction of class II molecules by PMA extends to the transcriptional level. Interestingly, anti-T112 and anti-T113 induced not only proliferation of T cells but also DR expression on more than 90% of T cells. These results indicate that transduction of a specific signal, probably selective phosphorylation of the CD3 molecule, contributes to class II MHC induction in the process of T cell activation.
Oshima
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Immunogenetics Research Section, Blood Center of Southeastern Wisconsin, Milwaukee 53233.
Eckels
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D000945:Antigens, Differentiation, T-Lymphocyte / Q000502:physiology*; D015152:Blotting, Northern; D018801:CD2 Antigens; D017252:CD3 Complex; D002453:Cell Cycle; D005434:Flow Cytometry; D015870:Gene Expression; D006681:HLA-D Antigens / Q000502:physiology*; D006684:HLA-DR Antigens / Q000235:genetics; D006801:Humans; D066298:In Vitro Techniques; D015759:Ionomycin / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D008285:Major Histocompatibility Complex; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D011971:Receptors, Immunologic / Q000502:physiology*; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000945:Antigens, Differentiation, T-Lymphocyte; D018801:CD2 Antigens; D017252:CD3 Complex; D006681:HLA-D Antigens; D006684:HLA-DR Antigens; D011948:Receptors, Antigen, T-Cell; D011971:Receptors, Immunologic; D015759:Ionomycin; D013755:Tetradecanoylphorbol Acetate