A Tcra congenic mouse: V alpha epitope expression is influenced by both Tcra haplotypes and background genes

Abstract

A T-cell receptor alpha chain locus (Tcra) congenic mouse is described. The Tcraa haplotype of BALB/c (donor strain) was bred on to B10.D2 (background strain, Tcrab haplotype) by using a Bgl I Tcra-C restriction fragment length polymorphism. Tcraa/b heterozygous offspring from the eleventh backcross generation were brother-sister mated to obtain Tcra-Ca homozygous animals. The resulting congenic line, B10.D2.C-Tcraa/Bo carries a recombination between the Tcra and the hr loci; thus, the transferred differential segment is the centromeric 18-27 cM of the BALB/c chromosome 14. Analysis with a multitude of Tcra-V and Tcrd-V probes demonstrates that the complete Tcraa haplotype is contained within this differential segment. Lymph node T cells of BALB/c (Tcraa) B10.D2 (Tcrab) and B10.D2.C-Tcraa were stained with anti-V alpha 8 (KT50, KT65), anti-V alpha 3.2 (RR3-16) and anti-V alpha 11.1 and 2 (RR8-1) monoclonal antibodies. We find that the frequencies of V alpha epitope expression are highly Tcra haplotype-dependent even though an influence of background genes is also observed. Thus, Tcra-V germline differences may possibly influence the T cell repertoire, in addition to the already well known positive and negative thymic selections. Tcra haplotype does not influence the frequencies of V beta utilization. However, BALB/c mice have fewer V beta 11+ T cells than B10.D2 and B10.D2-Tcraa, therefore, the BALB/c genome must harbor a V beta 11 deleting gene(s) in addition to those described so far.