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.
Turner
S J
SJ
Department of Pathology and Immunology, Monash Medical School, Prahran, Victoria, Australia.
Cose
S C
SC
Carbone
F R
FR
D000595:Amino Acid Sequence; D000818:Animals; D000956:Antigens, Viral; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D014644:Genetic Variation; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D018139:Simplexvirus / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014759:Viral Envelope Proteins / Q000276:immunology
D000956:Antigens, Viral; D017931:DNA Primers; D016693:Receptors, Antigen, T-Cell, alpha-beta; D014759:Viral Envelope Proteins; C040495:glycoprotein B, Simplexvirus