REGULATION OF THYMOCYTE DEVELOPMENT THROUGH CD3 - FUNCTIONAL DISSOCIATION BETWEEN P56(LCK) AND CD3-ZETA IN EARLY THYMIC SELECTION

We studied the extent of functional linkage between CD3 zeta and p56(lck) in pre-TCR-dependent thymocyte development. Differentiation of DN to DP cells was examined by treatment of RAG2/CD3 zeta and RAG1/p56(lck) double-deficient mice with anti-CD3 epsilon antibodies. The results suggest that CD3 zeta has no specific role in this maturation step, but may be important for amplification of signaling through the pre-TCR. In contrast, p56(lck) is the main protein tyrosine kinase associated with signaling through the pre-TCR-CD3 complex. In DP thymocytes, the Ca2+ response to anti-CDSE was totally abolished in CD3 zeta(-/-) but only reduced in p56(lck-/-) mice, and in vivo responses to anti-CD3 epsilon differed from one another. Thus, CD3 zeta and p56(lck) are functionally not tightly associated and their deficiencies cause distinct developmental defects.