Selection is not required to produce invariant T-cell receptor γ-gene junctional sequences

Abstract

RECOMBINATION of V-, D- and J-gene segments can generate an enormous diversity of T-cell antigen receptor (TCR) gene sequences^1,2. Although many γδ T cells fully exploit this diversification process, those in the epidermal and vaginal epithelium do not^3,4, predominantly expressing invariant γδ receptors in which the V–(D)–J junctional sequences in almost all the productive rearrangements are identical. The almost exclusive use of identical TCRs by cells in these sites is thought to reflect recognition of a stress-induced autologous antigen^5–8. To explain the prevalence of the invariant junctional sequences, it has been proposed that thymic selection operates on a population of originally diverse progenitor cells, resulting in a homogeneous repertoire^9,10. Alternatively the invariant sequences may result from biases in the recombination machinery in the fetal thymic progenitors of these cells^8,11,12. We report here the use of mice into which mutated TCR γ-gene rearrangement substrates have been introduced as transgenes to demonstrate directly that the canonical TCR Vγ3–Jγl and Vγ4–Jγl sequences occur at high frequency in the absence of the possibility of selection for the protein products.