USAGE OF HUMAN T-CELL RECEPTOR V-BETA, J-BETA, C-BETA AND V-ALPHA GENE SEGMENTS IS NOT PROPORTIONAL TO GENE NUMBER

Certain T-cell receptor (TCR) beta-chain variable (V), joining (J), and constant (C) gene segments, as well as TCRalpha-chain V gene segments, are disproportionally represented in TCR alpha and beta cDNA libraries derived from PHA-stimulated peripheral blood lymphocytes. Sequences of 138 TCRalpha clones and 96 TCRbeta clones were determined and of these 128 TCRalpha clones and 88 TCRbeta clones were found to contain unique combinations of V, J, and C gene segments or to display diversity in N region nucleotides. The frequency of the V, J, and C genes used in the assembly of unique transcripts was ascertained. Of the 24 reported Vbeta gene families, 21 were observed among the 88 TCRbeta clones including four Vbeta families (Vbeta1, Vbeta2, Vbeta3, and Vbeta4) that were represented in the sample 2 1/2-5 times more frequently than would be expected on the basis of copy number within the gene complex. Seventy-eight percent of the clones were positive for Cbeta2 and more than half of the clones (53%) used one of two Jbeta2 genes: Jbeta2.1 was present in 27 clones and Jbeta2.7 in 20 clones. TCR Valpha families were also disproportionately represented in this sample. Twenty-five of 30 Valpha families were observed in the sample of 128 clones including six recently reported Valpha families. Three Valpha families, Valpha2, Valpha8, and Valpha23, accounted for approximately 40% of the TCRalpha clones and were represented at 18%, 9.4%, and 13.3%, respectively. Both Valpha2 and Valpha8 gene families contain more than one gene; thus the number of clones observed in these families may, in part, be related to gene number. However, Valpha23, which appears to be a single-copy gene family, is significantly overrepresented in this sample. Although disproportional usage of Vbeta genes may be accounted for by superantigen exposure, reasons for disproportional usage of Jbeta, Cbeta, and Valpha genes are presently unknown.