Usage of human T-cell receptor Vβ, Jβ, Cβ, and Vα gene segments is not proportional to gene number

Abstract

Certain T-cell receptor (TCT) β-chain variable (V), joining (J), and constant (C) gene segments, as well as TCRα-chain V gene segments, are disproportionally represented in TCR α and β cDNA libraries derived from PHA-stimulated peripheral blood lymphocytes. Sequences of 138 TCRα clones and 96 TCRβ clones were determined and of these 128 TCRα clones and 88 TCRβ 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 Vβ genes, families, 21 were observed among the 88 TCRβ clones including four Vβ families (Vβ1, Vβ2, Vβ3, and Vβ4) 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 Cβ2 and more than half of the clones (53%) used one of two Jβ2 genes: Jβ2.1 was present in 27 clones and Jβ2.7 in 20 clones. TCR Vα families were also disproportionately represented in this sample. Twenty-five of 30 Vα families were observed in the sample of 128 clones including six recently reported Vα families. Three Vα families, Vα2, Vα8, and Vα23, accounted for ≈40% of the TCRα clones and were represented at 18%, 9.4%, and 13.3%, respectively. Both Vα2 and Vα8 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, Vα23, which appears to be a single-copy gene family, is significantly overrepresented in this sample. Although disproportional usage of Vβ genes may be accounted for by superantigen exposure, reasons for disproportional usage of Jβ, Cβ, and Vα genes are presently unknown.