Redistribution of critical major histocompatibility complex and T cell receptor-binding functions of residues in an antigenic sequence after biterminal substitution.
Residues critical for establishing a trimolecular interaction with a major histocompatibility complex (MHC)-encoded receptor and a T cell antigen receptor (TcR) were determined for an antigenic nonapeptide. The N-terminal residue proved to be involved in binding of the peptide to both receptors and the C-terminal residue was essential for MHC binding. While substitution of either of these critical terminal residues by alanine resulted in an almost complete loss of peptide antigenicity, simultaneous substitution of both created a new functional ligand for the same MHC molecule and the same TcR. Notably, in the biterminally substituted peptide, the core residues took on new roles in the trimolecular interaction in that a residue critical in the authentic nonapeptide for TcR binding became critical for MHC binding and former spacer residues became essential to various degrees for the interaction with either receptor or both. Thus, apparently, the loss of the terminal residues' contribution was at least partially compensated by a redistribution of the roles among the remaining residues. These results reflect a cooperative contribution of all residues of an antigenic peptide to its binding to both receptors and thus challenge a static definition of agretope and epitope as MHC and TcR binding sites.
Reddehase
M J
MJ
Department of Virology, Institute for Microbiology, University of Ulm, FRG.
Koszinowski
U H
UH
D000595:Amino Acid Sequence; D000818:Animals; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism*; D011487:Protein Conformation; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism*; D013329:Structure-Activity Relationship
D015395:Histocompatibility Antigens Class I; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell