1. Inability of bm14 mice to respond to Theiler's murine encephalomyelitis virus is caused by defective antigen presentation, not repertoire selection.
- Author
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Block MS, Mendez-Fernandez YV, Van Keulen VP, Hansen MJ, Allen KS, Taboas AL, Rodriguez M, and Pease LR
- Subjects
- Alleles, Amino Acid Sequence, Animals, CD8-Positive T-Lymphocytes immunology, CD8-Positive T-Lymphocytes virology, Cardiovirus Infections pathology, Demyelinating Diseases genetics, Demyelinating Diseases immunology, Demyelinating Diseases virology, 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 metabolism, T-Lymphocyte Subsets virology, Viral Proteins immunology, Viral Proteins metabolism, Antigen Presentation genetics, Cardiovirus Infections genetics, Cardiovirus Infections immunology, Genetic Predisposition to Disease, T-Lymphocyte Subsets immunology, Theilovirus immunology
- 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.
- Published
- 2005
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