The identification is made in normal mice of the stages in T cell development at which the rearranged p chain of the T cell receptor (TCR) is utilized to promote T cell maturation, independent of the TCRa chain. In addition, evidence is provided that utilization of ft chains in T cell progenitors does not preclude dlfferentiation to TCRy6+ T cells. This is consistent with the view that an initial consequence of fl chain expression by early thymocytes is clonal expansion, increasing the size of the pool of useful precursors. This allows the proposal to be made that allelic exclusion may be a byproduct of cell cycle regulation during early thymocyte differentiation, which may in turn explain why the efficiency of allelic exclusion varies at different TCR or immunoglobulin loci.

The predominant population of T lymphocytes in all adult vertebrates examined bears a heterodimeric T cell receptor (TCR) composed of a and j3 subunits. A numerically smaller population of thymocytes bears a heterodimeric yS TCR. As in the case of immunoglobulin, TCR chains are encoded by genes somatically rearranged from noncontiguous germline segments (Mak, 1992; Hayday, 1992). A major mechanism that effectively restricts a lymphocyte to a single specificity is thought to be allelic exclusion. The mechanism of allelic exclusion is poorly understood, but it apparently operates differently at different loci, being efficient at the TCR6 chain locus (von Boehmer, 1990) and at the immunoglobulin heavy chain locus (Weaver et al., 1965), but less effcient at the TCRa or y chain loci (Padovan et al., 1993; Davodeau et al., 1993) and the immunoglobulin K light chain locus (Feddersen et al., 1990).