MHC and non-MHC gene regulation of disease susceptibility and disease course in experimental inflammatory peripheral neuropathy.
With a panel of rat strains, we demonstrate a strong impact of the MHC genotype on susceptibility and disease course in experimental autoimmune neuritis induced with peripheral nerve myelin or the P2 peptide 58-81 (KNTEISFKLGQEFEETTADNRKTK). Beside the MHC genotype, non-MHC genes determined disease susceptibility and resistance. The type of disease induced with P2 58-81 was strongly correlated to the strength of the MHC class II isotype interaction with P2 58-81. These findings suggest a link between susceptibility and acute versus chronic disease courses on one hand and the strength of the MHC class II molecule/peptide affinity on the other hand.
de Graaf
Katrien L
KL
Experimental Neuroimmunology, Department of General Neurology, Centre for Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, Hoppe-Seyler-Strasse 3, 72076 Tübingen, Germany.
Wallström
Erik
E
Muhallab
Saad
S
Wiesmüller
Karl-Heinz
KH
Olsson
Tomas
T
Weissert
Robert
R
D000818:Animals; D002908:Chronic Disease; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000235:genetics* / Q000276:immunology; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D020275:Guillain-Barre Syndrome / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology; D006239:Haplotypes / Q000235:genetics; D006649:Histocompatibility Antigens / Q000235:genetics* / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology; D008297:Male; D018996:Myelin P2 Protein / Q000276:immunology; D009186:Myelin Sheath / Q000276:immunology; D009444:Neuritis, Autoimmune, Experimental / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology; D010446:Peptide Fragments / Q000276:immunology; D010523:Peripheral Nervous System Diseases / Q000235:genetics* / Q000276:immunology; D011485:Protein Binding / Q000235:genetics / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D011919:Rats, Inbred Strains; D013045:Species Specificity
D006649:Histocompatibility Antigens; D000949:Histocompatibility Antigens Class II; D018996:Myelin P2 Protein; D010446:Peptide Fragments