Influenza-specific cytotoxic T-cell recognition is inhibited by peptides unrelated in both sequence and MHC restriction.

Two related peptides from the nucleoprotein (NP) sequence 365-380, derived from influenza virus isolates A/PR/8/34 and A/NT/60/68, are recognized by mutually exclusive sets of Db (Class I)-restricted cytotoxic T-lymphocyte (CTL) clones. These peptides compete with each other for presentation on Db-bearing target cells in vitro. A Kk-restricted nucleoprotein epitope (NP 50-63), which is unrelated in sequence, competes more efficiently on H-2b target cells but is not itself recognized by virus-specific CTL from influenza-infected H-2b mice. A peptide sequence from the class I molecules Cw3 and Db can also compete, but additional unrelated peptides do not do so at equimolar concentrations. Our results show that competition is at the level of the target cell and imply that the binding specificity of the class I molecule Db is broader than indicated by the immune response phenotype of the C57BL (H-2b) mouse.