Human T-cell receptor variable gene segment families

Abstract

Multiple DNA and protein sequence alignments have been constructed for the human T-cell receptor alpha/delta, beta, and gamma (TCRA/D, B, and G) variable (V) gene segments. The traditional classification into subfamilies was confirmed using a much larger pool of sequences. For each sequence, a name was derived which complies with the standard nomenclature. The traditional numbering of V gene segments in the order of their discovery was continued and changed when in conflict with names of other segments. By discriminating between alleles at the same locus versus genes from different loci, we were able to reduce the number of more than 150 different TCRBV sequences in the database to a repertoire of only 47 functional TCRBV gene segments. An extension of this analysis to the over 100 TCRAV sequences results in a predicted repertoire of 42 functional TCRAV gene segments. Our alignment revealed two residues that distinguish between the highly homologous V delta and V alpha, one at a site that in VH contacts the constant region, the other at the interface between immunoglobulin VH and VL. This site may be responsible for restricted pairing between certain V delta and V gamma chains. On the other hand, V beta and V gamma appear to be related by the fact that their CDR2 length is increased by four residues as compared with that of V alpha/delta peptides.