IDENTIFICATION OF A TAP-DEPENDENT LEADER PEPTIDE RECOGNIZED BY ALLOREACTIVE T-CELLS SPECIFIC FOR A CLASS IB ANTIGEN

Recognition of the class Ib antigen Qa-1 by a portion of alloreactive cytotoxic T lymphocyte (CTL) clones requires that the target cell express a second gene, termed Qa-1 determinant modifier (Qdm). We show that Qdm is identical to most D allele genes, excepting D-k, and that a nonamer peptide derived from D alloantigens restores CTL. recognition on cells that lack the Qdm-encoded determinant. The equivalent D-k peptide has an Ala-->Val interchange at P3 and requires similar to 4 logs more peptide than the Ala(P3) peptide for target cell lysis. Two of five CTL clones, not dependent on Qdm for target cell recognition, also recognize the Qdm peptide as well as the Val(P3) variant. Although the adm peptide spans residues 3-11 from the leader, it requires the Tap transporters for its expression. Thus, the response against this class Ib molecule provides a tool for dissecting alloreactivity as well as pathways for antigen presentation.