Quantitation of lysozyme peptides bound to class II MHC molecules indicates very large differences in levels of presentation.
Knowing the abundance of peptides presented by MHC molecules is a crucial aspect for understanding T cell activation and tolerance. In this report we determined the relative abundance of four distinct peptide families after the processing of the model Ag hen egg-white lysozyme. The development of a sensitive immunochemical approach reported here made it possible to directly quantitate the abundance of these four epitopes presented by APCs, both in vitro and in vivo. We observed a wide range of presentation among these four different epitopes presented on the surface of APCs, with 250-fold differences or more between the most abundant epitope (48-63) and the least abundant epitopes. Importantly, we observe similar ratios of presentation from APCs in vitro as well as from APCs from the spleens and thymi of hen egg-white lysozyme transgenic mice. We discuss the relationship between the amount of peptide presented and their binding to I-A(k) molecules, immunogenicity, and tolerogenicity.
Velazquez
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Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
DiPaolo
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Unanue
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ER
D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation / Q000235:genetics; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D002645:Chickens; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D016056:Immunodominant Epitopes / Q000032:analysis; D016393:Lymphoma, B-Cell / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009113:Muramidase / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D011485:Protein Binding / Q000235:genetics / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology; D014407:Tumor Cells, Cultured
D000949:Histocompatibility Antigens Class II; C111388:I-Ak antigen; D016056:Immunodominant Epitopes; D010446:Peptide Fragments; C115854:hen egg lysozyme peptide (31-47); C400524:hen egg lysozyme peptide (48-61); C421864:hen egg lysozyme; C430583:hen egg lysozyme peptide (115-129); C430584:hen egg lysozyme peptide (18-33); D009113:Muramidase