Analysis of the interaction of peptide hen egg white lysozyme (34-45) with the I-Ak molecule.
We examined the structural characteristics of a peptide Ag that determine its ability to interact with class II-MHC molecules and TCR. The studies reported here focused on recognition of the hen egg white lysozyme (HEL) tryptic fragment HEL(34-45) by two I-Ak-restricted T cell hybridomas. HEL(34-45) bound to I-Ak created more than one antigenic specificity. Experiments with truncated peptides and alanine-substituted peptides indicated that two T cell hybrids either recognized distinct regions of the HEL(34-45) peptide, or different determinants generated by interaction of the peptide with I-Ak. Although we identified residues of HEL(34-45) that were critical to T cell recognition, no positions in the peptide were identified as I-Ak contact sites using single alanine substitutions. This suggests that more than one site or region of the peptide contributes to the binding to I-Ak. Finally, the murine lysozyme equivalent of 34-45 did not bind to I-Ak. Substitution of the corresponding murine lysozyme (self) residue at position 41 of HEL(34-45) abrogated I-Ak binding of the peptide.
Lambert
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Department of Pathology, Washington University School of Medicine, St. Louis, MO 63110.
Unanue
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D000409:Alanine; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D002645:Chickens; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D051379:Mice; D008969:Molecular Sequence Data; D009113:Muramidase / Q000276:immunology* / Q000378:metabolism; D010047:Ovalbumin / Q000276:immunology* / Q000378:metabolism; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
D000949:Histocompatibility Antigens Class II; D010446:Peptide Fragments; D010047:Ovalbumin; D009113:Muramidase; D000409:Alanine