SEQUENCE RESTRICTIONS IN T-CELL RECEPTOR BETA-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 alpha-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 V beta 8.3 region. In addition, the p2Ca-specific cells use almost exclusively one of three JP gene segments. Selection for these JP regions appears to be related to the presence of a glutamic acid residue that is encoded at the 5' end of the JP and is present within the CDR3. As p2Ca does not contain a complementary charged residue, this finding may suggest that the beta-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 V beta 8.3) and the CDR3 may each contact the L(d) molecule. In contrast to the V beta and J beta regions, the V beta D beta J beta junctions and V alpha J alpha 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.