The T cell receptor Vα11 gene family: Analysis of allelic sequence polymorphism and demonstration of Jα region-dependent recognition by allele-specific antibodies

Allelic polymorphism in TCR loci may play an important role in shaping the T cell repertoire and in disease susceptibility. We have used a combination of antibody and sequence analysis to investigate polymorphism in the murine Vα11 family. Two different antibodies have been analyzed that recognize particular Vα11 family members of the Vα^b and Vα(d) haplotypes. One antibody shows Jα dependency, suggesting a conformational element to the epitope. Investigation of the anti-Vα11 staining pattern on different mouse strains indicates that there is a marked influence of MHC haplotype on Vα11 selection and that Vα11 is preferentially expressed on CD4⁺ cells. Sequence analysis of Vα11 genes from the Vα^a, Vα^b, and Vα(d) haplotypes shows two potential regions for the haplotype-specific epitopes. The relatedness of the different Vα11 family members from different haplotypes suggests that the Vα11.1/11.2 gene duplication is relatively recent, but that Vα11.3 separated much earlier. Differences between Vα11.3 and Vα11.1/11.2 are concentrated in the putative complementarity determining regions (CDR), whereas differences between alleles are not clearly clustered. However, the Vα11.1^a and Vα11.1(d) alleles differ from Vα11.1^b and Vα11.2^b in CDR1. A Vα11.2-expressing anti-cytochrome c T cell has the same V-J junction as a Vα11.1-bearing cell with a similar fine specificity, indicating that Vα11.1^b and Vα11.2^b do not contribute different Ag specificities.