The T cell receptor repertoire of intestinal intraepithelial γδ T lymphocytes is influenced by genes linked to the major histocompatibility complex and to the T cell receptor loci

Most of the γδ T cells in the intestinal epithelium of normal mice use the Vγ1 or the Vγ7 gene segments. However, the relative proportions of γδ intraepithelial lymphocytes expressing either the Vγ1 or the Vγ7 chain vary among different strains of mice whereas they are quite constant between different individuals of the same strain, suggesting that genetic factors, rather than environmental factors, are responsible for the observed differences. To analyze the genetic factors influencing the representation of different γδ T cell subsets in the intestinal epithelium, we used available anti-T cell antigen receptor (TCR) V region-specific mAbs against Vγ1, Vγ4, Vγ7, and Vδ4 to examine the TCR repertoire of intraepithelial γδ lymphocytes in a set of (C57BL/6 × DBA/2) recombinant inbred strains. Our results show that the representation of different Vγ and Vδ gene products among γδ intestinal intraepithelial lymphocytes is under a complex genetic control with a marked influence by genes closely linked to the TCRγ, TCRδ, and major histocompatibility complex loci.