Preferential expression of TCR Vα regions in CD4/CD8 subsets: Class discrimination or co-receptor recognition?

The preferential expression of T-cell receptor (TCR) Vα regions in the CD4⁺ and CD8⁺ T-cell subsets suggests that they have a special role in distinguishing recognition of major histocompatibility complex (MHC) class I from class II, or CD4 from CD8. Here, Bee-Cheng Sim, David Lo and Nicholas Gascoigne review recent data indicating the molecular basis for this discrimination, and how polymorphism within Vα subfamilies and between TCR α-chain haplotypes contributes to the T-cell repertoire.