Cutting edge: Ly49A inhibits TCR/CD3-induced apoptosis and IL-2 secretion.
To evaluate the importance of Ly49A on TCR-induced cellular events, we established clones of the 1F2 T cell hybridoma expressing either Ly49A or a chimeric version, Ly49A/H, where the Ly49A cytoplasmic domain has been replaced by the Ly49H cytoplasmic domain. Ligation of Ly49A, but not Ly49A/H, with its ligand H-2D(d) or anti-Ly49A mAbs caused a specific inhibition of TCR/CD3-induced IL-2 secretion. Moreover, flow cytometry analysis of hypodiploid DNA and annexin V binding revealed that ligation of Ly49A protected cells from apoptosis induced by anti-CD3 mAbs or Ag. In contrast, ligation of the Ly49A/H chimeric receptor had no antiapoptotic effect. In addition, engagement of Ly49A selectively inhibited TCR-induced Fas ligand expression whereas TCR-induced Fas expression was not significantly affected. Expression of Ly49 inhibitory receptors on T cells may represent an important mechanism for the regulation of T cell survival in vivo by inhibiting TCR-induced apoptosis and IL-2 secretion.
Roger
J
J
Institut National de la Recherche Scientifique-Institut Armand-Frappier, Université du Québec, Laval, Quebec, Canada.
Chalifour
A
A
Lemieux
S
S
Duplay
P
P
D000818:Animals; D000950:Antigens, Ly; D017209:Apoptosis / Q000276:immunology*; D017252:CD3 Complex / Q000502:physiology; D002352:Carrier Proteins / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D016923:Cell Death / Q000276:immunology; D015536:Down-Regulation / Q000276:immunology; D053222:Fas Ligand Protein; D006825:Hybridomas; D007376:Interleukin-2 / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D037181:Lectins, C-Type; D008213:Lymphocyte Activation / Q000276:immunology; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D008565:Membrane Proteins / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D055650:NK Cell Lectin-Like Receptor Subfamily A; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000037:antagonists & inhibitors* / Q000502:physiology*; D055630:Receptors, NK Cell Lectin-Like; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000378:metabolism
D000950:Antigens, Ly; D017252:CD3 Complex; D002352:Carrier Proteins; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D007376:Interleukin-2; C527088:Klra1 protein, mouse; C527096:Klra8 protein, mouse; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D055650:NK Cell Lectin-Like Receptor Subfamily A; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D055630:Receptors, NK Cell Lectin-Like; D019014:fas Receptor