Expression and combinatorial diversity of germ line-encoded T cell receptor V genes in human peripheral blood T cells

Abstract

The potential diversity of the T cell receptor (TcR) is defined by the combinatorial expression of variable segments and by mechanisms that insert or delete nucleotides at the junctional regions. The available repertoire is strongly influenced by negative and positive selection events. To study whether the diversity of the human T cell receptor of peripheral T cells is further restricted by the interaction between the TcR α and β chains, we compared the level of transcription of different Va elements in human T cell blasts expressing either restricted or unrestricted sets of Vβ genes. Our data establish that in some individuals, but not in others, the transcription of a given Vα element is independent from the presence of particular Vβ transcripts. Furthermore, our data also suggest that, in contrast to mouse, major TcR V gene deletions are absent in humans. Taken collectively, these results indicate that the diversity of the peripheral human TcR repertoire can benefit from the combinatorial expression of all the V elements present in the genome.