title: C57BL/6 mice need MHC class II Aq to develop collagen-induced arthritis dependent on autoreactive T cells.
abstract: BACKGROUND
  Collagen-induced arthritis (CIA) has traditionally been performed in MHC class II A(q)-expressing mice, whereas most genetically modified mice are on the C57BL/6 background (expressing the b haplotype of the major histocompatibility complex (MHC) class II region). However, C57BL/6 mice develop arthritis after immunisation with chicken-derived collagen type II (CII), but arthritis susceptibility has been variable, and the immune specificity has not been clarified.
  
  
  OBJECTIVE
  To establish a CIA model on the C57BL/6 background with a more predictable and defined immune response to CII.
  
  
  RESULTS
  Both chicken and rat CII were arthritogenic in C57BL/6 mice provided they were introduced with high doses of Mycobacterium tuberculosis adjuvant. However, contaminating pepsin was strongly immunogenic and was essential for arthritis development. H-2(b)-restricted T cell epitopes on chicken or rat CII could not be identified, but expression of A(q) on the C57BL/6 background induced T cell response to the CII260-270 epitope, and also prolonged the arthritis to be more chronic.
  
  
  CONCLUSIONS
  The putative (auto)antigen and its arthritogenic determinants in C57BL/6 mice remains undisclosed, questioning the value of the model for addressing T cell-driven pathological pathways in arthritis. To circumvent this impediment, we recommend MHC class II congenic C57BL/6N.Q mice, expressing A(q), with which T cell determinants have been thoroughly characterised.
authors.affiliation: Medical Inflammation Research, Department of Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden. johan.backlund@ki.se
authors.forename: Johan
authors.initials: J
authors.lastname: Bäcklund
authors.forename: Cuiqin
authors.initials: C
authors.lastname: Li
authors.forename: Erik
authors.initials: E
authors.lastname: Jansson
authors.forename: Stefan
authors.initials: S
authors.lastname: Carlsen
authors.forename: Patrick
authors.initials: P
authors.lastname: Merky
authors.forename: Kutty-Selva
authors.initials: KS
authors.lastname: Nandakumar
authors.forename: Sabrina
authors.initials: S
authors.lastname: Haag
authors.forename: Jimmy
authors.initials: J
authors.lastname: Ytterberg
authors.forename: Roman A
authors.initials: RA
authors.lastname: Zubarev
authors.forename: Rikard
authors.initials: R
authors.lastname: Holmdahl
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000235:genetics* / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000276:immunology; D002645:Chickens; D024043:Collagen Type II / Q000276:immunology*; D004195:Disease Models, Animal; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005802:Genes, MHC Class II / Q000235:genetics*; D006239:Haplotypes; D007114:Immunization; D051379:Mice; D020297:Mice, Congenic; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D009161:Mycobacterium / Q000276:immunology; D051381:Rats; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D024043:Collagen Type II; D018984:Epitopes, T-Lymphocyte