A single T cell receptor recognizes structurally distinct MHC/peptide complexes with high specificity

The 2C T cell is a CD8⁺, alloreactive T cell, which recognizes cells bearing L(d) and K^bm3 class I major histocompatability complex molecules. Here, we characterize an allopeptide, designated dEV-8, that is a ligand in the K^bm3 molecule for the 2C TCR but is not a ligand in the L(d) molecule. By biochemical and immunological properties, dEV-8 is distinct from P2Ca, the L(d) allopeptide that is also recognized by the 2C TCR. Using the deduced amino acid sequence of dEV-8, we isolate a candidate endogenous source of the peptide. The endogenous protein, MLRQ, contains a peptide sequence identical to dEV-8. This degenerate recognition of two distinct peptide/MHC complexes by a single TCR has important implications for understanding allorecognition.