Sequence restrictions in T cell receptor β-chains that have specificity for a self-peptide/L^d complex

Cytotoxic T lymphocytes that react with a complex of L^d and a ubiquitous self-peptide derived from the enzyme α-ketoglutarate dehydrogenase (p2Ca, LSPFPFDL) can be readily elicited by the addition of synthetic peptide to cultures of BALB/c speen cells. As with other L^d restricted CTL, the p2Ca-specific cells use predominantly the Vβ8.3 region. In addition, the p2Ca-specific cells use almost exclusively one of three Jβ gene segments. Selection for these Jβ regions appears to be related to the presence of a glutamic acid residue that is encoded at the 5' end of the Jβ and is present within the CDR3. As p2Ca does not contain a complementary charged residue, this finding may suggest that the β-chain CDR3 from p2Ca-specific CTL contacts one of the five basic residues located on the L^d helices. Together, the results support the possibility that CDR1 and/or CDR2 (within Vβ8.3) and the CDR3 may each contact the L^d molecule. In contrast to the Vβ and Jβ regions, the VβDβJβ junctions and Vα Jα repertoires were diverse. The diversity could explain why p2Ca-specific CTL have relatively high precursor frequencies allowing them to be generated rapidly in primary cultures.