In humans, the T cell repertoire is influenced by HLA, T cell receptor null alleles and antigen. Here, we describe a novel mechanism, independent of superantigen or T cell receptor structure which influences the T cell repertoire in a V beta-dependent manner. We have identified a biallelic locus, the TCRBV13S2 T cell receptor gene, where allelic differences predominate in the non-coding regions including transitions, transversions and frameshift deletions. The expressed protein is non-polymorphic at this locus. The TCRBV13S2 genotype profoundly influences the circulating levels of V beta 13.2 CD4 T cells but does not affect T cell receptor expression or function.