Alloreactive 2C T cells recognize a self peptide in the context of the mutant K^bm3 molecule

Previous studies have shown that 2C T cells have dual specificity for L^d and K^bm3 alloantigens and are positively selected in the context of Kb. Analysis of K^bm3-eluted peptides reveals a single HPLC fraction that is a central component of the K^bm3 allodeterminant. Peptides with biologic and biochemical properties indistinguishable from those of the K^bm3 allopeptide were also isolated from K^b and K^bm8, despite the fact that cells bearing these class I molecules are not efficient targets for 2C T cells. The allopeptide was isolated and compared with p2Ca, the L^d allopeptide recognized by 2C T cells in the context of L^d. The K^bm3 allopeptide was found to be biochemically and functionally different from p2Ca. Therefore, the 2C TCR has dual specificity for two different peptides presented in the context of two structurally distinct class I molecules. The possibility of a common peptide being bound by K^b, K^bm3, and K^bm8 suggests that the peptide defined as an allodeterminant in the context of K^bm3 may also function in the positive selection of 2C T cells when presented in the context of Kb and K^bm8 during thymic development. In support of this view, the allopeptide was also found in K^b and K^bm8 thymic peptide eluates.