Profile of Numbers of Sequence Differences Among V-Genes Coding for the Variable Regions of T Cell Receptor for Antigen Alpha and Beta Chains

Abstract. When human T cell receptor for antigen (TCR) alpha chain V-genes were compared pair-wise, the numbers of nucleotide differences showed a characteristic distribution; most were in the range of 100 to 200 differences out of a total of about 300 bases. The same distribution was observed for mouse TCR alpha chains. Even more interesting was that comparing human alpha chains and mouse alpha chains gave essentially the same nucleotide difference pattern. It is inferred from the large number of differences and from the nonspecificity of trans-species (human and mouse) nucleotide sequence differences of TCR V-genes that TCR alpha chains probably diverged early during evolution. The same feature was also observed for human and mouse TCR beta chains, although the alpha and beta chain V-genes were distinct. This evolutionary preservation could be of vital importance to the fidelity of the complicated trimolecular interactions among TCR alpha and beta chains, the processed peptide, and the major histocompatibility complex (MHC) class I or II molecules.

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