Parental genes do not codominantly confer susceptibility to experimental autoimmune encephalomyelitis in F1 rats.
Lewis (LEW) and DA rats are highly susceptible to experimental autoimmune encephalomyelitis (EAE) induced with guinea pig myelin basic protein (MBP), but respond to different epitopes. The dominant epitope for LEW rats is MBP73-86, and disease is mediated primarily by Vbeta8.2 Th1 cells. DA rats lack conventional Vbeta8.2 T cells and do not respond to MBP73-86. Rather, DA rats respond to the cryptic epitope MBP63-81, which is not encephalitogenic for LEW rats. Responses to these neuroantigens were investigated in (DAxLEW) F1 hybrids to determine if experimental findings in inbred rats remain valid in more genetically complex models. Surprisingly, MBP63-81, a cryptic epitope for DA rats, induced moderate-to-severe EAE in F1 hosts, whereas MBP73-86, the dominant LEW epitope, was only weakly encephalitogenic in F1 hosts. The poor clinical response to MBP73-86 appears to be a consequence of an inability to expand Vbeta8.2 T cells. These results suggest that parental responses to neuroantigens are poor predictors for determining encephalitogenicity in F1 progeny.
Lenz
D C
DC
Department of Immunology and Microbiology, Wayne State University School of Medicine, Detroit, MI 48201, USA. dlenz@med.wayne.edu
Wolf
N A
NA
Swanborg
R H
RH
D019264:Adoptive Transfer; D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D002455:Cell Division / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics* / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D020022:Genetic Predisposition to Disease; D016056:Immunodominant Epitopes / Q000276:immunology; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000378:metabolism; D008969:Molecular Sequence Data; D004676:Myelin Basic Protein / Q000737:chemistry / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016056:Immunodominant Epitopes; D004676:Myelin Basic Protein; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma