MHC class I antigens regulate CD3-induced tyrosine phosphorylation of proteins in T cells.
The MHC class I antigens enhance the T cell response to various mitogenic stimuli. Class I antigens co-cap and associate with the CD3 structure on these cells. The present work shows that co-aggregation of these MHC antigens with CD3 induces a sustained elevated Ca2+ response in T cells. The duration required for a 50% decline in peak response is five to 10 times longer when class I antigens are cross-linked with CD3 as compared to that when cells are stimulated through CD3 alone. Further analysis reveals that class I antigens prolong the duration of CD3-induced tyrosine phosphorylation of several proteins. No protein tyrosine kinase activity is found associated with these MHC antigens which could explain their influence on CD3 activation. Similarly, class I antigens do not depend on the membrane-bound protein tyrosine phosphatase CD45, since they elevate the degree of CD3-induced Ca2+ response in a CD45-deficient Jurkat cell line. On the contrary, in a CD45- HPB cell line defective in CD3 signaling, co-aggregation of class I antigens with CD3 does not induce Ca2+ flux. Therefore, the effect of class I antigens on CD3 function depends on the ability of CD3 to transduce a signal. Furthermore, cytofluorometric studies show that cross-linking of class I antigens with CD3 inhibits the internalization of the latter. Thus, class I antigens seem to prolong the duration of signal transduction through CD3 by retarding its down-regulation.
Dasgupta
J D
JD
Department of Pathology, Harvard Medical School, Dana-Farber Cancer Institute, Boston, MA 02115.
Granja
C B
CB
Yunis
E J
EJ
Relias
V
V
D017252:CD3 Complex / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000502:physiology*; D006801:Humans; D015151:Immunoblotting; D007424:Intracellular Fluid / Q000378:metabolism; D010766:Phosphorylation; D011233:Precipitin Tests; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000201:enzymology* / Q000276:immunology*; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism*
D017252:CD3 Complex; D015395:Histocompatibility Antigens Class I; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D002118:Calcium