title: Evidence of selective processing of immunodominant epitopes in virally infected cells.
abstract: Recent advances in clarifying the molecular mechanisms involved in Ag processing and presentation have relied heavily on the use of somatic cell mutants deficient in proteasome subunits, TAP transporter, and cell surface expression of MHC class I molecules. Of particular interest currently are those mutants that lack specific protease activity involved in the generation of antigenic peptides. It is theoretically possible that deficiencies of this nature could selectively prevent the cleavage of certain peptide bonds and thus generate only a subset of antigenic peptides. Gro29/Kb cell line is derived from the wild-type murine Ltk- cell line. This cell line is one example of a mutant that lacks specific protease activities. This deficiency manifests itself in an inability to generate a subset of immunodominant peptide epitopes derived from vesicular stomatitis virus and herpes simplex virus. This in turn leads to a general inability to present these viral epitopes to cytotoxic T lymphocytes (CTL). These studies describe a unique Ag processing deficiency and provide new insight into the role of proteasome-independent proteases in MHC class I-restricted peptide generation.
authors.affiliation: Biotechnology Laboratory and Biomedical Research Centre, Medical Genetics and Zoology, University of British Columbia, Vancouver, Canada.
authors.forename: Q J
authors.initials: QJ
authors.lastname: Zhang
authors.forename: S S
authors.initials: SS
authors.lastname: Chen
authors.forename: C A
authors.initials: CA
authors.lastname: Saari
authors.forename: M G
authors.initials: MG
authors.lastname: Massuci
authors.forename: F
authors.initials: F
authors.lastname: Tufaro
authors.forename: W A
authors.initials: WA
authors.lastname: Jefferies
mesh_terms: D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D000818:Animals; D017951:Antigen Presentation / Q000235:genetics / Q000276:immunology*; D000956:Antigens, Viral / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000096:biosynthesis; D018984:Epitopes, T-Lymphocyte / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000276:immunology; D006183:H-2 Antigens / Q000096:biosynthesis / Q000235:genetics; D016056:Immunodominant Epitopes / Q000378:metabolism*; D007739:L Cells; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D009097:Multienzyme Complexes / Q000096:biosynthesis; D019251:Nucleocapsid / Q000172:deficiency / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D019590:Nucleocapsid Proteins; D010455:Peptides / Q000276:immunology / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D018139:Simplexvirus / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism* / Q000821:virology*; D014721:Vesicular stomatitis Indiana virus / Q000276:immunology; D014759:Viral Envelope Proteins / Q000172:deficiency / Q000235:genetics
chemical_list: D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; D000956:Antigens, Viral; D018984:Epitopes, T-Lymphocyte; D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; D016056:Immunodominant Epitopes; D009097:Multienzyme Complexes; D019590:Nucleocapsid Proteins; D010455:Peptides; C073119:TAP1 protein, human; C486171:Tap1 protein, mouse; D014759:Viral Envelope Proteins; C489300:LTK protein, human; C064626:Ltk protein, mouse; D020794:Receptor Protein-Tyrosine Kinases; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex