TCR alpha-chain usage can determine antigen-selected TCR beta-chain repertoire diversity

There is considerable variation in the TCR repertoire diversity selected by different peptide Ags. Certain responses show limited V region bias with minimal restrictions in the remainder of the sequence while others can be dominated by a single TCR clonotype repeatedly isolated from different individuals. CTL specific for a Kb-restricted determinant from the herpes simplex virus glycoprotein B (gB) preferentially express a dominant TCRBV10 beta-chain subset with extensive conservation located at the V-D junction. However, unlike some biased responses, no single beta-chain V-D-J combination appears to dominate these CTL. Different animals respond with a large array of unique or "private" beta-chain sequences with little J region preference. Here we examine the contribution of the TCR alpha-chain to the gB-specific CTL diversity. The TCR alpha-chains from different TCRBV10-positive gB-specific CTL clones were found to exhibit extensive sequence variation. However, when T cells were forced to use a single alpha-chain in TCR alpha-chain transgenic mice, gB-specific CTL showed limited variation in their beta-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 consisted of the transgenic alpha-chain and a common TCRBV10D2J2S6 beta-chain. 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.