GENETIC AND IMMUNOCHEMICAL EVIDENCE FOR CD4-DEPENDENT ASSOCIATION OF P56(LCK) WITH THE ALPHA-BETA-T-CELL RECEPTOR (TCR) - REGULATION OF TCR-INDUCED ACTIVATION

Recent observations suggest that the tyrosine kinase p56(lck) is involved in the transduction of transmembrane signals throught the antigen specific T cell receptor (TCR) in CD4(+) T cells. By means of in vitro kinase assays, we have found the p56(lck) coprecipitated with the TCR from lysates of a murine CD4(+) T cell line in the absence of TCR-mediated stimuli. Analysis of CD4(-) mutants and CD4-transfected cells shows that p56(lck)- TCR association occurred only when CD4 was present. The functional importance of CD4:p56(lck)-TCR association was demonstrated by low activating potential of rare clonotypic antibodies which did not coprecipitate CD4:p56(lck), as well asy by total or partial loss of anti-TCR or antigen induced stimulation of CD4(-) cells, which could be recovered by CD4 transfection. Complementation assays using different anti-TCR antibodies suggest that cross linking of TCR-p56(lck):CD4 plus structural changes in the complex are needed for efficient transduction of activating signals through the TCR in these cells.