Variability and repertoire size of T-cell receptor V_α gene segments

Abstract

The immune system of higher organisms is composed largely of two distinct cell types, B lymphocytes and T lymphocytes, each of which is independently capable of recognizing an enormous number of distinct entities through their antigen receptors; surface immunoglobulin in the case of the former, and the T-cell receptor (TCR) in the case of the latter. In both cell types, the genes encoding the antigen receptors consist of multiple gene segments which recombine during maturation to produce many possible peptides^1–9. One striking difference between B- and T-cell recognition that has not yet been resolved by the structural data is the fact that T cells generally require a major histocompatibility determinant together with an antigen^10,11 whereas, in most cases, antibodies recognize antigen alone. Recently, we and others have found that a series of TCR V_β gene sequences^12,13 show conservation of many of the same residues that are conserved between heavy- and light-chain immunoglobulin V regions, and these Vβ sequences are predicted to have an immunoglobulin-like secondary structure^12,13. To extend these studies, we have isolated and sequenced eight additional α-chain complementary cDNA clones and compared them with published^14–16 sequences. Analyses of these sequences, reported here, indicate that V_α regions have many of the characteristics of V_β gene segments but differ in that they almost always occur as cross-hybridizing gene families. We conclude that there may be very different selective pressures operating on V_α and V_β sequences and that the V_α repertoire may be considerably larger than that of V_β.