TCR ALPHA-CHAIN USAGE CAN DETERMINE ANTIGEN-SELECTED TCR BETA-CHAIN REPERTOIRE DIVERSITY

There is considerable variation in the TCR repertoire diversity select ed by different peptide Ags, Certain responses show limited V region b ias with minimal restrictions in the remainder of the sequence while o thers can be dominated by a single TCR clonotype repeatedly isolated f rom different individuals, CTL specific for a K-b-restricted determina nt from the herpes simplex virus glycoprotein B (gB) preferentially ex press a dominant TCRBV10 beta-chain subset with extensive conservation located at the V-D junction, However, unlike some biased responses, n o single beta-chain V-D-J combination appears to dominate these CTL. D ifferent animals respond with a large array of unique or ''private'' b eta-chain sequences with little J region preference, Here we examine t he contribution of the TCR alpha-chain to the gB-specific CTL diversit y, The TCR alpha-chains from different TCRBV10-positive gB-specific CT L clones were found to exhibit extensive sequence variation, However, when T cells were forced to use a single alpha-chain in TCR alpha-chai n transgenic mice, gB-specific CTL showed limited variation in their b eta-chain selection, These T cells retained the TCRBV10 bias but were now dominated by a single beta-chain sequence that could be repeatedly isolated from different transgenic animals, This ''public'' TCR consi sted of the transgenic alpha-chain and a common TCRBV10D2J2S6 beta-cha in, These results suggest that preferential use of one TCR subunit can restrict the level of diversity in the other chain due to interchain interactions involving J-derived sequences.