Studies on the human T cell receptor alpha/beta variable region genes. II. Identification of four additional V beta subfamilies.

The human T cell receptor (TcR) beta chain gene segment diversity has been studied using the anchored-polymerase chain reaction. Three hundred and fifty C beta-specific transcripts derived from peripheral lymphocytes were analyzed. Transcripts including V-D beta 1-J beta 2-C2 sequences were found with a high frequency (greater than 10%), suggesting that "illegitimate" joinings may constitute a cis-complementing rearrangement mechanism capable of substantially increasing the TcR beta chain combinatorial diversity. Twelve previously undescribed V beta gene segments have been identified. Five of them delineate four novel V beta subfamilies (V beta w21: two members, V beta w22, 23, 24: one member) which all have a murine homologue. The additional seven gene segments belong to the V beta 5, V beta 6, V beta 12 and V beta 13 subfamilies. In addition, the sequences of two known V beta 7 and V beta 9 gene segments have been extended. Together, the present data support the view that the contribution of the beta chain combinatorial diversity to the TcR alpha/beta variability has not yet been fully appreciated.