C57BL/6 mice need MHC class II Aq to develop collagen-induced arthritis dependent on autoreactive T cells.

Abstract

INTRODUCTION:

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: Johan Bäcklund, Cuiqin Li, Erik Jansson, Stefan Carlsen, Patrick Merky, Kutty-Selva Nandakumar, Sabrina Haag, Jimmy Ytterberg, Roman A Zubarev, Rikard Holmdahl
• Journal: Annals of the rheumatic diseases (Ann Rheum Dis) Vol. 72 Issue 7 Pg. 1225-32 (Jul 2013) ISSN: 1468-2060 [Electronic] England
• PMID: 23041839 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Collagen Type II
• Epitopes, T-Lymphocyte

Topics

• Animals
• Arthritis, Experimental (genetics, immunology)
• Arthritis, Rheumatoid (genetics, immunology)
• Chickens
• Collagen Type II (immunology)
• Disease Models, Animal
• Epitopes, T-Lymphocyte (immunology)
• Genes, MHC Class II (genetics)
• Haplotypes
• Immunization
• Mice
• Mice, Congenic
• Mice, Inbred C57BL
• Mice, Inbred Strains
• Mycobacterium (immunology)
• Rats
• T-Lymphocytes (immunology)