Functional consequences of a T cell receptor D beta 2 and J beta 2 gene segment deletion

The TCR beta-chain locus of NZW mice carries an 8.8-kb deletion which encompasses the C beta 1, D beta 2, and all six J beta 2 gene segments. On a theoretical basis, the absence of D beta 2 and J beta 2 gene segments in this strain should result in a 70% reduction of the diversity of the TCR repertoire. To experimentally assess the effects of this deletion, we bred the NZW TCR beta-chain allele onto a BALB/c background and tested the ability of this new congenic strain to respond to a panel of 22 random Ag. T cells from BALB/c.beta NZW mice responded to all 22 Ag tested but the magnitude of the response to a large proportion of these Ag (11 of 22) was markedly reduced when compared with T cells from BALB/c mice. Responses to the remaining Ag were either comparable (9 of 22) or occasionally even enhanced (2 of 22) compared with BALB/c mice. In addition, we found that the frequency of V beta 6- and V beta 8.1-bearing T cells was increased by approximately 20% in BALB/c.beta NZW mice. These results suggest that D beta 2 and J beta 2 gene segments are required to maintain a diverse T cell repertoire and that their deletion from the genome may confer a significant selective disadvantage in the wild.