title: Inability of bm14 mice to respond to Theiler's murine encephalomyelitis virus is caused by defective antigen presentation, not repertoire selection.
abstract: Natural selection drives diversification of MHC class I proteins, but the mechanism by which selection for polymorphism occurs is not known. New variant class I alleles differ from parental alleles both in the nature of the CD8 T cell repertoire formed and the ability to present pathogen-derived peptides. In the current study, we examined whether T cell repertoire differences, Ag presentation differences, or both account for differential viral resistance between mice bearing variant and parental alleles. We demonstrate that nonresponsive mice have inadequate presentation of viral Ag, but have T cell repertoires capable of mounting Ag-specific responses. Although previous work suggests a correlation between the ability to present an Ag and the ability to generate a repertoire responsive to that Ag, we show that the two functions of MHC class I are independent.
authors.affiliation: Department of Immunology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Block
authors.forename: Yanice V
authors.initials: YV
authors.lastname: Mendez-Fernandez
authors.forename: Virginia P
authors.initials: VP
authors.lastname: Van Keulen
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Hansen
authors.forename: Kathleen S
authors.initials: KS
authors.lastname: Allen
authors.forename: Anya L
authors.initials: AL
authors.lastname: Taboas
authors.forename: Moses
authors.initials: M
authors.lastname: Rodriguez
authors.forename: Larry R
authors.initials: LR
authors.lastname: Pease
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation / Q000235:genetics*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D018188:Cardiovirus Infections / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D003711:Demyelinating Diseases / Q000235:genetics / Q000276:immunology / Q000821:virology; D020022:Genetic Predisposition to Disease; D006183:H-2 Antigens / Q000235:genetics / Q000378:metabolism; D064532:Histocompatibility Antigen H-2D; D007113:Immunity, Innate / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding / Q000235:genetics / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D017945:Theilovirus / Q000276:immunology*; D014764:Viral Proteins / Q000276:immunology / Q000378:metabolism
chemical_list: D006183:H-2 Antigens; D064532:Histocompatibility Antigen H-2D; D010446:Peptide Fragments; D014764:Viral Proteins