Inability of bm14 mice to respond to Theiler's murine encephalomyelitis virus is caused by defective antigen presentation, not repertoire selection

J Immunol. 2005 Mar 1;174(5):2756-62. doi: 10.4049/jimmunol.174.5.2756.

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alleles
  • Amino Acid Sequence
  • Animals
  • Antigen Presentation / genetics*
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / virology
  • Cardiovirus Infections / genetics*
  • Cardiovirus Infections / immunology*
  • Cardiovirus Infections / pathology
  • Demyelinating Diseases / genetics
  • Demyelinating Diseases / immunology
  • Demyelinating Diseases / virology
  • Genetic Predisposition to Disease*
  • H-2 Antigens / genetics
  • H-2 Antigens / metabolism
  • Histocompatibility Antigen H-2D
  • Immunity, Innate / genetics
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Mutant Strains
  • Molecular Sequence Data
  • Peptide Fragments / immunology
  • Peptide Fragments / metabolism
  • Protein Binding / genetics
  • Protein Binding / immunology
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism
  • T-Lymphocyte Subsets / virology
  • Theilovirus / immunology*
  • Viral Proteins / immunology
  • Viral Proteins / metabolism

Substances

  • H-2 Antigens
  • Histocompatibility Antigen H-2D
  • Peptide Fragments
  • Viral Proteins