title: Promiscuous binding of extracellular peptides to cell surface class I MHC protein.
abstract: Algorithms derived from measurements of short-peptide (8-10 mers) binding to class I MHC proteins suggest that the binding groove of a class I MHC protein, such as K(b), can bind well over 1 million different peptides with significant affinity (<500 nM), a level of ligand-binding promiscuity approaching the level of heat shock protein binding of unfolded proteins. MHC proteins can, nevertheless, discriminate between similar peptides and bind many of them with high (nanomolar) affinity. Some insights into this high-promiscuity/high-affinity behavior and its impact on immunodominant peptides in T-cell responses to some infections and vaccination are suggested by results obtained here from testing a model developed to predict the number of cell surface peptide-MHC complexes that form on cells exposed to extracellular (exogenous) peptides.
authors.affiliation: Koch Institute for Integrative Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA. hneisen@mit.edu
authors.forename: Herman N
authors.initials: HN
authors.lastname: Eisen
authors.forename: Xun Helen
authors.initials: XH
authors.lastname: Hou
authors.forename: Chase
authors.initials: C
authors.lastname: Shen
authors.forename: Kaidi
authors.initials: K
authors.lastname: Wang
authors.forename: Varsha Keelara
authors.initials: VK
authors.lastname: Tanguturi
authors.forename: Crysela
authors.initials: C
authors.lastname: Smith
authors.forename: Katerina
authors.initials: K
authors.lastname: Kozyrytska
authors.forename: Lakshmi
authors.initials: L
authors.lastname: Nambiar
authors.forename: Carol A
authors.initials: CA
authors.lastname: McKinley
authors.forename: Jianzhu
authors.initials: J
authors.lastname: Chen
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Cohen
mesh_terms: D000818:Animals; D001665:Binding Sites; D002462:Cell Membrane / Q000378:metabolism; D004705:Endocytosis; D005805:Genes, MHC Class I; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D020128:Inhibitory Concentration 50; D007700:Kinetics; D008024:Ligands; D051379:Mice; D008954:Models, Biological; D010047:Ovalbumin / Q000737:chemistry; D010455:Peptides / Q000737:chemistry; D011485:Protein Binding; D011489:Protein Denaturation; D017510:Protein Folding; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D015395:Histocompatibility Antigens Class I; D008024:Ligands; D010455:Peptides; D010047:Ovalbumin