title: HLA-F and MHC-I open conformers cooperate in a MHC-I antigen cross-presentation pathway.
abstract: Peptides that are presented by MHC class I (MHC-I) are processed from two potential sources, as follows: newly synthesized endogenous proteins for direct presentation on the surface of most nucleated cells and exogenous proteins for cross-presentation typically by professional APCs. In this study, we present data that implicate the nonclassical HLA-F and open conformers of MHC-I expressed on activated cells in a pathway for the presentation of exogenous proteins by MHC-I. This pathway is distinguished from the conventional endogenous pathway by its independence from TAP and tapasin and its sensitivity to inhibitors of lysosomal enzymes, and further distinguished by its dependence on MHC-I allotype-specific epitope recognition for Ag uptake. Thus, our data from in vitro experiments collectively support a previously unrecognized model of Ag cross-presentation mediated by HLA-F and MHC-I open conformers on activated lymphocytes and monocytes, which may significantly contribute to the regulation of immune system functions and the immune defense.
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
authors.forename: Jodie P
authors.initials: JP
authors.lastname: Goodridge
authors.forename: Ni
authors.initials: N
authors.lastname: Lee
authors.forename: Aura
authors.initials: A
authors.lastname: Burian
authors.forename: Chul-Woo
authors.initials: CW
authors.lastname: Pyo
authors.forename: Scott S
authors.initials: SS
authors.lastname: Tykodi
authors.forename: Edus H
authors.initials: EH
authors.lastname: Warren
authors.forename: Cassian
authors.initials: C
authors.lastname: Yee
authors.forename: Stanley R
authors.initials: SR
authors.lastname: Riddell
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Geraghty
mesh_terms: D000595:Amino Acid Sequence; D000954:Antigens, Surface / Q000276:immunology; D000956:Antigens, Viral / Q000737:chemistry / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D045744:Cell Line, Tumor; D045142:Cross-Priming; D011992:Endosomes / Q000187:drug effects / Q000201:enzymology / Q000276:immunology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000939:Epitopes / Q000276:immunology; D018984:Epitopes, T-Lymphocyte; D015395:Histocompatibility Antigens Class I / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000276:immunology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000473:pathology; D018448:Models, Immunological; D008969:Molecular Sequence Data; D009000:Monocytes / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D011487:Protein Conformation; D021381:Protein Transport; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
chemical_list: D000954:Antigens, Surface; D000956:Antigens, Viral; D004791:Enzyme Inhibitors; D000939:Epitopes; D018984:Epitopes, T-Lymphocyte; C062341:HLA-F antigens; D015395:Histocompatibility Antigens Class I; D010446:Peptide Fragments