Distinct involvement of CD45 in antigen receptor signalling in CD4+ and CD8+ primary T cells.
We demonstrate that pretreatment of primary CD4+, but not CD8+ T cells with anti-CD45 inhibits activation signals induced through the T cell receptor for antigen (TCR alpha beta). Specifically, anti-TCR alpha beta-mediated tyrosine phosphorylation of phospholipase C-gamma 1 is inhibited, and this in turn correlates with the inhibition of subsequent Ca2+ mobilization and DNA synthesis. In marked contrast, none of these activation parameters are affected by anti-CD45 in CD8+ T cells. Perturbation of TCR alpha beta signalling in CD4+ cells is observed in conditions which do not detectably affect the level of CD45 expression, or its membrane distribution. Further, changes in the intrinsic phosphatase activity of CD45 are not detectable. While anti-CD45 ablates TCR alpha beta signalling, anti-CD3 epsilon-mediated activation is unaffected. This suggests that elements of the antigen receptor complex can be functionally uncoupled, and indicates that the requirements for CD45 in signalling through these two elements are different. The results demonstrate that the involvement of CD45 in coupling TCR alpha beta to second messenger-generating pathways is under distinct physical and/or functional constraints in primary CD4+ and CD8+ T cells.
Maroun
C R
CR
Department of Microbiology and Immunology, McGill University, Montreal, Canada.
Julius
M
M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D016827:CD8 Antigens / Q000032:analysis*; D002118:Calcium / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000502:physiology*; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D051379:Mice; D008807:Mice, Inbred BALB C; D010716:Phosphatidylinositols / Q000378:metabolism; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000502:physiology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000502:physiology*; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000502:physiology*
D000911:Antibodies, Monoclonal; D016827:CD8 Antigens; D010716:Phosphatidylinositols; D011518:Proto-Oncogene Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D017493:Leukocyte Common Antigens; D017027:Protein Tyrosine Phosphatases; D002118:Calcium