title: Processing pathways for presentation of cytosolic antigen to MHC class II-restricted T cells.
abstract: Antigens presented to CD4+ T cells derive primarily from exogenous proteins that are processed into peptides capable of binding to class II major histocompatibility complex (MHC) molecules in an endocytic compartment. In contrast, antigens presented to CD8+ T cells derive mostly from proteins processed in the cytosol, and peptide loading onto class I MHC molecules in an early exocytic compartment is dependent on a transporter for antigen presentation encoded in the class II MHC region. Endogenous cytosolic antigen can also be presented by class II molecules. Here we show that, unlike class I-restricted recognition of antigen, HLA-DR1-restricted recognition of cytosolic antigen occurs in mutant cells without a transporter for antigen presentation. In contrast, DR1-restricted recognition of a short cytosolic peptide is dependent on such a transporter. Thus helper T-cell epitopes can be generated from cytosolic antigens by several mechanisms, one of which is distinct from the classical class I pathway.
authors.affiliation: Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland 20852.
authors.forename: M S
authors.initials: MS
authors.lastname: Malnati
authors.forename: M
authors.initials: M
authors.lastname: Marti
authors.forename: T
authors.initials: T
authors.lastname: LaVaute
authors.forename: D
authors.initials: D
authors.lastname: Jaraquemada
authors.forename: W
authors.initials: W
authors.lastname: Biddison
authors.forename: R
authors.initials: R
authors.lastname: DeMars
authors.forename: E O
authors.initials: EO
authors.lastname: Long
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D015704:CD4 Antigens / Q000276:immunology; D016827:CD8 Antigens / Q000276:immunology; D002872:Chromosome Deletion; D003600:Cytosol / Q000276:immunology; D005805:Genes, MHC Class I; D005802:Genes, MHC Class II; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006389:Hemagglutinins, Viral / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D010957:Plasmids; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014162:Transfection; D014616:Vaccinia virus / Q000235:genetics
chemical_list: D015704:CD4 Antigens; D016827:CD8 Antigens; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006389:Hemagglutinins, Viral; D009838:Oligodeoxyribonucleotides