A Possible Basis for Major Histocompatibility Complex-Restricted T-Cell Recognition

Abstract

Four distinct T-cell antigen-receptor gene loci have now been identified and partly characterized: ɑ, β, y and δ. All of these loci can rearrange in an immunoglobulin- like fashion and express polypeptides that contribute to either ɑ:β or y:δ T-cell receptor-CD3 complexes. Surprisingly, the T-cell receptor (TCR) δ coding regions are located entirely, or almost entirely, within the TCR ɑ locus and share at least some of the V region gene segments, thus at least partly linking the two different types of receptor heterodimers. Analysis of potential T-cell receptor diversity, particularly that of the δ chain, indicates a striking concentration of somatic polymorphism in the V-J junctional region of the two heterodimers, four to six orders of magnitude higher than similar calculations for immunoglobulin light- and heavy-chain combinations. In contrast, the number of possible V region combinations in T-cell receptors is one hundredth to one thousandth that of immunoglobulins. TCR ɑ:β heterodimers are known to recognize many possible fragments of antigens embedded in the peptide- binding clefts of a relatively small number of major histocompatibility complex (MHC) molecules. Thus it is attractive to speculate that the V-J junctional portions of both types of T-cell receptor contact peptide antigens, whereas the remaining diversity regions contact the MHC. This contention is supported by molecular modelling studies and has interesting implications for the evolution of antigen-receptor genes.