A role for peptide in determining MHC class II structure.
T lymphocytes recognize antigen-derived peptides associated with major histocompatibility complex (MHC) class I or class II proteins. Peptide is critical in class I heavy-chain folding and/or stable association with beta 2-microglobulin. Although data exist suggesting a relationship between class II structure and peptide association, no equivalent positive contribution of peptide to the folding state or stability of class II dimers has yet been demonstrated. We report here that most purified E alpha k E beta k molecules leaving low pH in the absence of specific peptide lack a compact, stable dimeric structure. Brief exposure to the appropriate peptide just before and during neutralization promotes this specific conformation in proportion to stably bound peptide, indicating that peptide is important in determining class II MHC structure. Our results also indicate that efficient generation of long-lived peptide-class II complexes involves two stages: initial peptide binding in an acidic environment, which enhances the ability of class II to enter a conformation, from which stabilization upon neutralization results in high-affinity binding of previously associated peptide.
Sadegh-Nasseri
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Lymphocyte Biology Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892.
Germain
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D000818:Animals; D000941:Antigens / Q000378:metabolism; D003580:Cytochromes / Q000737:chemistry; D000949:Histocompatibility Antigens Class II / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D008024:Ligands; D051379:Mice; D009113:Muramidase / Q000737:chemistry / Q000276:immunology; D010047:Ovalbumin / Q000737:chemistry / Q000276:immunology; D010455:Peptides / Q000502:physiology*; D011485:Protein Binding; D011487:Protein Conformation; D011499:Protein Processing, Post-Translational
D000941:Antigens; D003580:Cytochromes; D000949:Histocompatibility Antigens Class II; C024138:I-E-antigen; D008024:Ligands; D010455:Peptides; D010047:Ovalbumin; D009113:Muramidase