Signals delivered via MHC class II molecules synergize with signals delivered via TCR/CD3 to cause proliferation and cytokine gene expression in T cells.
We examined the role of MHC class II molecules in transducing signals to activated human T cells. Cross-linking of MHC class II molecules synergized with submitogenic amounts of anti-CD3 mAb in causing proliferation and secretion of the cytokines IL-2, IL-3, IFN-gamma, and TNF-alpha by MHC class II-alloreactive T cell lines. Signaling via MHC class II molecules in T cells resulted in activation of tyrosine kinases, in generation of inositol phosphates, and in Ca2+ mobilization that was abrogated by the tyrosine kinase inhibitor herbimycin A. Thus, like signaling via TCR/CD3, signaling via MHC class II molecules involved tyrosine kinase-dependent activation of phospholipase C, resulting in phosphoinositol turnover and Ca2+ flux. However the signaling pathways coupled to MHC class II molecules and to TCR/CD3 differed, because engagement of the transmembrane phosphatase CD45 inhibited Ca2+ fluxes triggered via TCR/CD3 but not Ca2+ fluxes triggered via MHC class II molecules.
Spertini
F
F
Division of Immunology, Children's Hospital, Boston, MA 02115.
Chatila
T
T
Geha
R S
RS
D015703:Antigens, CD / Q000502:physiology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000502:physiology*; D016227:Benzoquinones; D017252:CD3 Complex; D002118:Calcium / Q000378:metabolism; D016207:Cytokines / Q000235:genetics*; D015870:Gene Expression; D006681:HLA-D Antigens / Q000502:physiology*; D006649:Histocompatibility Antigens / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000378:metabolism; D047029:Lactams, Macrocyclic; D017493:Leukocyte Common Antigens; D008213:Lymphocyte Activation; D019000:Phosphotyrosine; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011809:Quinones / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D011940:Receptor Aggregation; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D017828:Rifabutin / Q000031:analogs & derivatives; D015290:Second Messenger Systems; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000502:physiology*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D016227:Benzoquinones; D017252:CD3 Complex; D016207:Cytokines; D006681:HLA-D Antigens; D006649:Histocompatibility Antigens; D007295:Inositol Phosphates; D047029:Lactams, Macrocyclic; D011809:Quinones; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; D017828:Rifabutin; D019000:Phosphotyrosine; D014443:Tyrosine; C020754:herbimycin; D011505:Protein-Tyrosine Kinases; D017493:Leukocyte Common Antigens; D002118:Calcium