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 e ncephalomyelitis (EAE) induced with guinea pig myelin basic protein (MBP), but respond to different epitopes. The dominant epitope for LEW rats is MBP 73-86, and disease is mediated primarily by V beta8.2 Th1 cells. DA rats la ck conventional V beta8.2 T cells and do not respond to MBP73-86. Rather, D A rats respond to the cryptic epitope MBP63-81, which is not encephalitogen ic for LEW rats. Responses to these neuroantigens were investigated in (DAX LEW) F1 hybrids to determine if experimental findings in inbred rats remain valid in more genetically complex models. Surprisingly, MBP63-81, a crypti c 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 o f an inability to expand V beta8.2 T cells. These results suggest that pare ntal responses to neuroantigens are poor predictors for determining encepha litogenicity in F1 progeny. (C) 2001 Elsevier Science B.V. All rights reser ved.