Inability of bm14 mice to respond to Theiler's murine encephalomyelitis virus is caused by defective antigen presentation, not repertoire selection.
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.
Block
Matthew S
MS
Department of Immunology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
Mendez-Fernandez
Yanice V
YV
Van Keulen
Virginia P
VP
Hansen
Michael J
MJ
Allen
Kathleen S
KS
Taboas
Anya L
AL
Rodriguez
Moses
M
Pease
Larry R
LR
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
D006183:H-2 Antigens; D064532:Histocompatibility Antigen H-2D; D010446:Peptide Fragments; D014764:Viral Proteins