title: HLA class I polymorphism has a dual impact on ligand binding and chaperone interaction.
abstract: This article will describe coordinated analyses of how amino acid substitutions in the HLA class I antigen binding groove modify chaperone interaction and peptide ligand presentation. By parallel testing of ligand presentation and chaperone interaction with a series of natural HLA-B subtypes, this study has discovered that position 116 of the HLA-B15 class I heavy chain is pivotal in both peptide selection and control of interaction between the assembly complex and the class I heavy chain. Correlated with these qualitative differences in peptide selection and chaperone association are quantitative differences in the expression levels of the HLA molecules at the cell surface. These parallel studies, therefore, demonstrate that particular HLA class I polymorphisms can simultaneously influence ligand presentation and interaction with intracellular chaperones.
authors.affiliation: Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
authors.forename: William H
authors.initials: WH
authors.lastname: Hildebrand
authors.forename: Heth R
authors.initials: HR
authors.lastname: Turnquist
authors.forename: Kiley R
authors.initials: KR
authors.lastname: Prilliman
authors.forename: Heather D
authors.initials: HD
authors.lastname: Hickman
authors.forename: Erin L
authors.initials: EL
authors.lastname: Schenk
authors.forename: Mary M
authors.initials: MM
authors.lastname: McIlhaney
authors.forename: Joyce C
authors.initials: JC
authors.lastname: Solheim
mesh_terms: D015235:HLA-B Antigens / Q000235:genetics / Q000276:immunology*; D059910:HLA-B15 Antigen; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D008024:Ligands; D018832:Molecular Chaperones / Q000276:immunology*; D010455:Peptides / Q000276:immunology; D011110:Polymorphism, Genetic
chemical_list: D015235:HLA-B Antigens; D059910:HLA-B15 Antigen; D015395:Histocompatibility Antigens Class I; D008024:Ligands; D018832:Molecular Chaperones; D010455:Peptides