A method of estimating the numbers of human and mouse T cell receptors for antigen alpha and beta chain V-genes.

T cell receptors for antigen (TCR) V-genes are under a very restrictive evolutionary pressure in order to maintain their biological activities of interacting with MHC class I or II molecules and processed peptides at the protein level. This is in contrast to immunoglobulin V-genes which can mutate more freely. As we have discussed before, 17 or less nucleotide differences between any two mouse lambda light chain V-genes can be due to somatic mutations induced by antigens, allelic variations, and the combination of these two mechanisms. Thus, a cut-off of 17 nucleotide differences has been used to estimate the numbers of the other human and mouse immunoglobulin chain V-genes. Except for mouse heavy chains where experimental study is not yet available, our estimated numbers are in good agreement with experimental findings. For TCR V-genes, however, this cut-off value should be modified as illustrated in the present analysis. Our estimation of the number of human TCR beta chain V-genes is also in good agreement with the recent experimental study of sequencing 685 kb of that gene locus. Estimations for the numbers of human alpha, mouse alpha and beta chain V-genes will wait for future experimental verification.