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.
Babbitt
B P
BP
Matsueda
G
G
Haber
E
E
Unanue
E R
ER
Allen
P M
PM
D000595:Amino Acid Sequence; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D000941:Antigens / Q000276:immunology*; D001667:Binding, Competitive; D003902:Detergents; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D008051:Lipid Bilayers; D008264:Macrophages / Q000276:immunology; D051379:Mice; D009113:Muramidase / Q000276:immunology* / Q000378:metabolism; D009842:Oligopeptides / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding; D013329:Structure-Activity Relationship
D000941:Antigens; D003902:Detergents; D000949:Histocompatibility Antigens Class II; D008051:Lipid Bilayers; D009842:Oligopeptides; D009113:Muramidase