PHYSICAL ASSOCIATION OF CD4 AND CD45 IN PRIMARY, RESTING CD4(-CELLS()T)

CD45 is a family of transmembrane protein tyrosine phosphatases that a re essential to T lymphocytes' responses to antigen-receptor stimulati on. It is involved in the regulation of Src-family protein tyrosine ki nases, Lck and Fyn. The object of this study was to determine how CD45 molecules are directed to such substrates at the antigen-receptor com plex upon stimulation of resting T cells. We demonstrate that CD45 is physically associated with CD4 in resting, primary lymph node T cells. Further, CD4-dependent, antigen-mediated activation of primary CD4(+) T cells results in disruption of CD4-CD45 complexes, suggesting a rol e for these complexes in the activation process. Moreover, CD45 coprec ipitates with CD4 molecules which are associated with Lck, as well as with those which are not associated with Lck. Consistent with these ob servations and the role of CD45 in the regulation of Lck function, eff ects on CD4-associated membrane Lck are demonstrable. Since antigen pr esentation by MHC class II results in the coaggregation of CD4 with th e antigen-receptor complex, the association described in this study pr ovides a physical basis through which CD45 could be included. (C) 1997 Academic Press