Regulation of Transcription of the Human T Cell Antigen Receptor S Chain Gene a T Lineage-specific Enhancer Element Is Located in the J63-c6 Intron

T cells recognize antigens using a clonally expressed TCR, TCRa/0, whose genes undergo somatic rearrangements during the early stages of thymic differentiation. The a/S heterodimer is expressed in noncovalent association with the CD3 complex at the cell surface of the great majority of mature thymocytes and peripheral T cells. Another CD3-associated heterodimer, y/S, was found to be expressed by a minority of typically CD4-CD8"-thymocytes and peripheral T cells (1-7). It has been shown that TCR-y and-S genes undergo rearrangement during the earliest phase of T cell differentiation. Although rearrangements of TCR,y/b genes are generally considered to be T cell specific, frequent inappropriate rearrangements ofthese genes have been documented in early B cell leukemias. Such findings are uncommonly found in chronic B cell proliferations (8, 9). The organization ofboth TCRy and-S genes has been established. In both genes the germline-encoded repertoire appears to be limited, and most of the diversity is due to nucleotide additions and/or deletions at V(D) J junctions (10). To date, six V4 three DS, three JS, and one CS segments have been described (11-14). One VS segment, VS3, is located 3' to Cb and rearranges by inversion (Fig. 1 A, top). Considerable evidence has recently demonstrated that CD3-y/$ like the CD3-alR, functions as an antigen receptor. The antigen repertoire of this TCR has not yet been fully defined, but it has been established that at least a subset of'Y/S-expressing lymphoid cells are involved in the primary response against mycobacterial antigens (15). It is generally thought that a/(3-and y/6-expressing cells belong to distinct T cell lineages. The mechanisms involved in the choice between the a/0 vs. y/S lineage remain