The homogeneity of the TCRdelta repertoire expressed by the Thy-1dull gammadelta T cell population is due to cellular selection

Abstract

Thy-1dull gammadelta T cells are an unusual subset of mature TCRgammadelta T cells characterized by their highly restricted TCR repertoire. In DBA/2 mice, they predominantly express the product of the Vgamma1 gene together with that of a member of the Vdelta6 subfamily (the Vdelta6.4 gene) and their junctional sequences show very little diversity. To address the mechanisms underlying the expression of the restricted TCRgammadelta repertoire, we have cloned all Vdelta6 subfamily members present in DBA/2 mice and studied their frequency of expression in Thy-1dull and Thy-1bright gammadelta thymocyte populations. Furthermore, we have also cloned non-functional Vdelta6DdeltaJdelta1 rearrangements present in the Thy-1dull gammadelta T cell population and compared their Vdelta6 gene utilization and their junctional sequences with those expressed by this population. Our results indicate that the restricted TCRdelta repertoire expressed by the Thy-1dull gammadelta thymocytes results from cellular selection, rather than molecular constraints suggesting the existence of a limited set of self-ligands. Finally, phenotypic, functional and TCRgammadelta repertoire analysis of Thy-1dull gammadelta T cells in beta2-microglobulin (beta2m)-deficient mice indicated that these putative ligands are not beta2m-dependent major histocompatibility complex class I or class I-like molecules.