THE HOMOGENEITY OF THE TCR-DELTA REPERTOIRE EXPRESSED BY THE THY-1(DULL) GAMMA-DELTA T-CELL POPULATION IS DUE TO CELLULAR-SELECTION

Thy-1(dull) gamma delta T cells are an unusual subset of mature TCR ga mma delta T cells characterized by their highly restricted TCR reperto ire. In DBA/2 mice, they predominantly express the product of the V ga mma 1 gene together with that of a member of the V delta 6 subfamily ( the V delta 6.4 gene) and their junctional sequences show very little diversity. To address the mechanisms underlying the expression of the restricted TCR gamma delta repertoire, we have cloned all V delta 6 su bfamily members present in DBA/2 mice and studied their frequency of e xpression in Thy-1(dull) and Thy-1(bright) gamma delta thymocyte popul ations. Furthermore, we have also cloned non-functional V delta 6D del ta J delta 1 rearrangements present in the Thy-1(dull) gamma delta T c ell population and compared their V delta 6 gene utilization and their junctional sequences with those expressed by this population. Our res ults indicate that the restricted TCR delta repertoire expressed by th e Thy-1(dull) gamma delta thymocytes results from cellular selection, rather than molecular constraints suggesting the existence of a limite d set of self-ligands. Finally, phenotypic, functional and TCR gamma d elta repertoire analysis of Thy-1(dull) gamma delta T cells in (beta 2 -microglobulin (beta(2)m)-deficient mice indicated that these putative ligands are not pgm-dependent major histocompatibility complex class I or class I-like molecules.