Early human T cell activation events with engagement of surface MHC class II.
Major histocompatibility complex (MHC) class II are expressed on most activated human lymphocytes. They direct antigen presentation events in dendritic cells and B cells (collectively called antigen presenting cells), but the role for MHC class II in human T cells is not well understood. To understand the role of surface MHC class II and to identify the molecules involved in signaling, we have defined the early activation sequence in T cells when MHC class II are engaged by a specific antibody. Specifically, we have characterized the involvement of phosphotyrosine kinases, phospholipase C (PLC), and Ca2+ mobilization. With the engagement by either whole anti-class II antibody or its Fab fragments, the enzymatic activity of p56lck and ZAP-70 increased, but there was no increase in p59fyn activity. In addition, the intracellular free Ca2+ increased, which was due to enhanced influx and not to the mobilization of intracytoplasmic Ca2+. These events did not require cross-linking because they were not significantly augmented by the addition of antispecies antibody. The coimmunoprecipitation of tyrosine phosphorylated PLC-gamma1 with surface MHC class II suggested that PLC-gamma1 could be recruited to MHC class II after engagement. These results show the complexities of the early signals transduced by the engagement of surface MHC class II on T cells.
Department of Pediatrics, State University of New York Health Science Center, Syracuse 13210, USA.
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Nguyen
D000911:Antibodies, Monoclonal / Q000378:metabolism / Q000494:pharmacology; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D000949:Histocompatibility Antigens Class II / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000378:metabolism / Q000494:pharmacology; D007527:Isoenzymes / Q000378:metabolism; D019169:Jurkat Cells; D008213:Lymphocyte Activation; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000378:metabolism; D051966:Phospholipase C gamma; D010835:Phytohemagglutinins / Q000494:pharmacology; D011233:Precipitin Tests; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051076:Proto-Oncogene Proteins c-fyn; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D010738:Type C Phospholipases / Q000378:metabolism; D051746:ZAP-70 Protein-Tyrosine Kinase
D000911:Antibodies, Monoclonal; D000949:Histocompatibility Antigens Class II; D007140:Immunoglobulin Fab Fragments; D007527:Isoenzymes; D010835:Phytohemagglutinins; D011518:Proto-Oncogene Proteins; D011505:Protein-Tyrosine Kinases; C494957:FYN protein, human; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D051076:Proto-Oncogene Proteins c-fyn; D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human; D010738:Type C Phospholipases; D051966:Phospholipase C gamma; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium