Comparative analysis of collagen type II-specific immune responses during development of collagen-induced arthritis in two B10 mouse strainsReport as inadecuate

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Arthritis Research and Therapy

, 14:R237

First Online: 01 November 2012Received: 18 June 2012Revised: 19 September 2012Accepted: 22 October 2012


IntroductionImmune responses against collagen type II CII are crucial for the development of collagen-induced arthritis CIA. The aim of the present study was to evaluate and compare the CII-directed T cell and antibody specificity at different time points in the course of CIA using two mouse strains on the B10 genetic background - B10.Q, expressing A MHC class II molecules, and B10.DR4.Ncf1, expressing human rheumatoid arthritis-associated MHC II DR4 molecules DRA*0101-DRB*0401.

MethodsB10.Q and B10.DR4.Ncf1 mice were immunized with CII emulsified in adjuvant and development of CIA was assessed. T cells from draining lymph nodes were restimulated in vitro with CII peptides and interferon-gamma IFN-γ levels in culture supernatants were evaluated by ELISA. CII-specific antibody levels in serum samples were measured by ELISA.

ResultsAt four different CIA time points we analyzed T cell specificity to the immunodominant CII epitope 259-273 CII259-273 and several posttranslationally modified forms of CII259-273 as well as antibody responses to three B cell immunodominant epitopes on CII C1, U1, J1. Our data show that CII-specific T and B cell responses increase dramatically after disease onset in both strains and are sustained during the disease course. Concerning anti-CII antibody fine specificity, during all investigated stages of CIA the B10.Q mice responded predominantly to the C1 epitope, whereas the B10.DR4.Ncf1 mice also recognized the U1 epitope. In the established disease phase, T cell reactivity toward the galactosylated CII259-273 peptide was similar between the DR4- and the A-expressing strains whereas the response to the non-modified CII peptide was dramatically enhanced in the DR4 mice compared with the B10.Q. In addition, we show that the difference in the transgenic DR4-restricted T cell specificity to CII259-273 is not dependent on the degree of glycosylation of the collagen used for immunization.

ConclusionsThe present study provides important evaluation of CII-specific immune responses at different phases during CIA development as well as a comparative analysis between two CIA mouse models. We indicate significant differences in CII T cell and antibody specificities between the two strains and highlight a need for improved humanized B10.DR4 mouse model for rheumatoid arthritis.

AbbreviationsABTS2,2-azino-bis3-ethylbenzothiazoline-6-sulphonic acid

CIAcollagen-induced arthritis

CIIcollagen type II

conAconcanavalin A

DELFIAdissociation-enhanced lanthanide fluoroimmunoassay

DPBSDulbecco-s phosphate-buffered saline

ELISAenzyme-linked immunosorbent assay

huCIIhuman collagen type II


IgGimmunoglobulin G


MHC IImajor histocompatibility complex class II

RArheumatoid arthritis

rCIIrat collagen type II

RTroom temperature.

Electronic supplementary materialThe online version of this article doi:10.1186-ar4080 contains supplementary material, which is available to authorized users.

Tsvetelina Batsalova, Ingrid Lindh contributed equally to this work.

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Author: Tsvetelina Batsalova - Ingrid Lindh - Johan Bäcklund - Balik Dzhambazov - Rikard Holmdahl


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