Signals delivered via the Qa-2 molecule can synergize with limiting anti-CD3-induced signals to cause T lymphocyte activation.
Qa-2 is a glycolipid anchored, MHC encoded class I molecule expressed at high levels on all murine peripheral T lymphocytes. Anti-Qa-2 antibodies have previously been found to stimulate T cells to proliferate in the presence of crosslinking antibody and PMA. We have examined the effect of anti-Qa-2 antibodies on T cells stimulated with a suboptimal concentration of immobilized anti-CD3. When anti-Qa-2 antibodies were co-immobilized with limiting anti-CD3, in the absence of PMA, a clear augmentation of T cell proliferation was seen. Interestingly, the co-stimulatory anti-Qa-2 antibodies could be directed against epitopes mapped to either the alpha 3 or the alpha 1/alpha 2 Qa-2 domains. As was the case with activation induced by soluble/crosslinked anti-Qa-2 antibodies plus PMA, CD8+ T cells were less able to be costimulated with anti-Qa-2 antibodies than CD4+ cells. Surprisingly, Ca2+ mobilization was only seen when two anti-Qa-2 antibodies reactive to separate structural domains were co-crosslinked on the surface of Indo-1 loaded T cells with a suboptimal concentration of anti-CD3. Collectively these results raise questions regarding the mechanism of Qa-2 mediated signaling and its potential role in T cell activation.
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
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Hahn
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Tian
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Wiegand
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Soloski
D000818:Animals; D000906:Antibodies / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D000954:Antigens, Surface / Q000276:immunology; D017252:CD3 Complex; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000276:immunology; D051379:Mice; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D018800:Thy-1 Antigens
D000906:Antibodies; D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface; D017252:CD3 Complex; D015395:Histocompatibility Antigens Class I; D008562:Membrane Glycoproteins; C032907:Q surface antigens; D011948:Receptors, Antigen, T-Cell; D018800:Thy-1 Antigens; D002118:Calcium