hen antibodies to T-cell receptor (TCR) V␣ regions first became available, it was clear that there was a bias in expression of individual V␣ region family members between the CD4 ϩ or CD8 ϩ peripheral T-cell subsets 1,2 . This has held true for all of the mouse, human and rat V␣ regions analyzed to date. As this selective influence is generally not dependent on major histocompatibility complex (MHC) allotype, it was suggested that certain V␣ members interact better with either one or the other co-receptor, or with MHC class I or class II molecules. There is much variability within each V␣ family, and sequence differences correlate with differential expression in the peripheral T-cell subsets. This article discusses the recently revealed structures of TCR-MHC class I and CD8-MHC class I complexes, and CD4 dimers, in relation to V-region selection. Evidence is reviewed linking V-region selection with MHC or co-receptor interactions and the effect of V␣ polymorphism on MHC class discrimination and the overall T-cell repertoire.
Polymorphism: V␣ families and haplotypes
In the mouse, there are five ␣-locus (Tcra) haplotypes distinguished on the basis of restriction fragment length polymorphisms (RFLPs; reviewed in Ref. 3). Among the common laboratory strains, BALB/c, CBA, C3H and A/J have the Tcra a haplotype; the C57 strains have Tcra b ; nonobese diabetic (NOD), NZB, SJL and SWR have Tcra c ; the Tcra d haplotype is carried by NZW and DBA; and Tcra e , apparently a recombination of Tcra a and Tcra b , is found only in RIII/Rd. The haplotypes differ in their number and organization of V-gene elements, owing to separate duplication events in different parts of the locus. This has caused different members of the same V␣ family to be interspersed throughout the locus, where the individual genes have diverged from each other. Overall, the V␣ locus is rife with instability, since sub-lines of the same mouse strain frequently have RFLP differences.