MAJOR HISTOCOMPATIBILITY COMPLEX AND T-CELL RECEPTOR INTERACTION OF THE P91A TUM(-) PEPTIDE

The P91A antigen was identified following mutation of P1 mastocytoma c ells. The peptide epitope is encoded by a mutant form of the S3 subuni t of the PA700 proteasome regulatory complex. P91A stimulates a strong CD8(+) T cell response when expressed on tumor cells or normal tissue and P91A-specific T cells express a restricted range of T cell recept ors. Although it is a strong L(d)-binding peptide, P91A does not confo rm to the established motif for this major histocompatibility complex (MHC) molecule and this has hampered elucidation of the precise epitop e. L(d) predominantly associates with nonamer peptides; however, using a variety of complementary approaches, the P91A epitope is identified as the octamer QNHRALDL. In the absence of the L(d) motif residue pro line at position 2, residues 5-7 are primarily involved in MHC interac tion. P91A is thus atypical in its interaction with L(d). Residues 1, 3, and 4 are found to influence T cell recognition of P91A. Definition of the P91A peptide will allow studies on P91A processing and interac tions of the P91A peptide/MHC complex with T cell receptors of differi ng avidity to establish the basis for restricted T cell receptor usage . The basis for the failure of the P91A tum(+) peptide (QNRRALDL) to b ind to L(d) is addressed by molecular modeling.