Antigenic competition at the level of peptide-Ia binding

We examined the direct binding of a hen egg white lysozyme peptide, HEL(46-61), to membrane I-Ak (protein encoded in the A locus of the I region) molecules in the presence of detergent. A number of synthetic peptide derivatives, which did not stimulate our T-cell reactive hybridomas, competed for the binding of HEL(46-61) to I-Ak and also inhibited the functional presentation of HEL(46-61). Inhibitors included a peptide lacking a tyrosine at position 53 and a peptide corresponding to the autologous lysozyme peptide. Presentation was examined with cells or with supported planar phospholipid membranes bearing only I-Ak and HEL(46-61). Other Peptides that did not compete for the binding did not inhibit functional presentation. We concluded that the binding of an immunogenic peptide to I-A is critical for presentation, that the I-A molecule does not discriminate between autologous and foreign related determinants but does recognize structurally different Peptides. Our evidence suggests that our immunogenic peptide bears noncontiguous Amino acids critical for contact I-A binding interspersed with Amino acids critical for interaction with T cells.