title: HLA-B polymorphisms and intracellular assembly modes.
abstract: Human leukocyte antigen (HLA) class I molecules are ligands for antigen receptors of cytotoxic T cells (CTL) and inhibitory receptors of natural killer (NK) cells. The high degree of HLA class I polymorphism allows for the selection of distinct and diverse sets of antigenic peptide ligands for presentation to CTL. The extensive polymorphisms of the HLA class I genes also result in large variations in their intracellular folding and assembly characteristics. Recent findings indicate that North American HLA-B variants differ significantly in the stabilities of their peptide-deficient forms and in the requirements for the endoplasmic reticulum (ER)-resident factor tapasin for proper assembly. In HIV-infected individuals, the presence of tapasin-independent HLA-B allotypes links to more rapid progression to death. Further studies are important to better understand how the intrinsic structural characteristics of HLA class I folding intermediates affect immune responses mediated by CTL and NK cells.
authors.affiliation: Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109, USA. Electronic address: malinir@umich.edu.
authors.forename: Malini
authors.initials: M
authors.lastname: Raghavan
authors.affiliation: Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Geng
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000235:genetics*; D000938:Antigen-Presenting Cells / Q000166:cytology / Q000276:immunology*; D003600:Cytosol / Q000276:immunology / Q000378:metabolism; D015235:HLA-B Antigens / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology; D026901:Membrane Transport Proteins / Q000235:genetics / Q000276:immunology; D008958:Models, Molecular; D010455:Peptides / Q000276:immunology / Q000378:metabolism; D011110:Polymorphism, Genetic; D055607:Receptors, Natural Killer Cell / Q000235:genetics / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology
chemical_list: D015235:HLA-B Antigens; D026901:Membrane Transport Proteins; D010455:Peptides; D055607:Receptors, Natural Killer Cell; C107762:tapasin
keywords: AIDS; Calreticulin; ERp57; Endoplasmic reticulum; HIV; HLA-B; MHC class I; Peptide loading complex; TAP transporter; Tapasin