Immunogenetics of collagen-induced arthritis in rats. Both MHC and non-MHC gene products determine the epitope specificity of immune response to bovine and chick type II collagens.

Abstract

Seven inbred, RT1-congenic rat strains were immunized with native bovine (BII), porcine (PII), or chick (CII) type II collagen and observed for onset, incidence, and severity of arthritis. Clinical results were compared with IgG reactive with native rat type II collagen (RII) and the purified, renatured cyanogen-bromide peptides of BII, CII, or RII. Immunodominant responses to CB11, CB9,7, and CB12 of RII were identified. Secondary responses to CB8 and CB10 also occurred. Reproducible patterns of peptide reactivity were defined in each strain and reflected both RT1 and non-RT1 genotypes plus the species of immunizing collagen. BN non-RT1 gene products moderated clinical arthritis but increased the levels of reactivity to CB11 in three strains carrying RT1l,n,av1 haplotypes. WF (RT1u) rats were susceptible to collagen-induced arthritis (CIA) and developed very high levels of autoantibodies with dominant responses to rat CB11 after CII injections and to rat CB11 and CB9,7 after BII injections. DA (RT1av1) rats developed the most severe arthritis but had only moderate (total) levels of anti-RII IgG: a broad response to CB11, CB10, and CB9,7 after CII injections but predominantly to CB12 and CB9,7 after BII injections. Three RT1n strains--DA.1N(BN), WF.1N(MAXX), and BN--were resistant to BII-induced CIA but developed mild arthritis after immunization with CII. After BII: BN IgG reacted with CB9-7, CB11, and CB12; DA.1N and WF.1N IgG reacted with CB9,7 and CB12. After CII: BN IgG reacted broadly with CB11, CB9-7, CB12, and CB8; WF.1N IgG reacted to CB9-7, CB11, CB8, and CB12; DA.1N IgG reacted with CB8, CB11, and CB9-7. Thus, selective induction of CIA in BN, WF.1N, and DA.1N rats by CII correlated with serum IgG reactivity to rat CB11, but overall strain results identified no single cyanogen-bromide peptide as expressing the sole "arthritogenic" epitope in CIA.

C-Terminal Region of Caveolin-3 Contains a Stretch of Amino Acid Residues Capable of Diminishing Symptoms of Experimental Autoimmune Encephalomyelitis but Not Rheumatoid Arthritis Modeled in Rats

“…Despite the variety of rat strains bearing different MHC types that are susceptible to collagen II-induced arthritis, the incidence rate, magnitude of symptoms, and CIA severity could be different. This also includes antibodies and the scope of the T-cell reactive epitope specificity [28][29][30].…”

“…This point makes a bridge between the features of the autoimmune disease model and the antigenic specificity of the MHC proteins in the animals used for modeling the disease [28,29]. It is known that rat strains with different MHC types are able to develop CIA, although the autoantibody specificities or T-cell epitope affinities may differ among the rat strains significantly [30]. For instance, DA and SD rats have distinct MHC RT1 haplotypes av1 and f respectively [25,29].…”

Collagen‐Induced Arthritis

“…Arthritic responses to chick and bovine CII are often equivalent, with the notable exception of ACI and BN rats where disparate responses are seen. Studies by Griffiths et al (1992) have also shown that the arthritis-producing potential of porcine CII is essentially identical to that of bovine and human CII.…”

“…Arthritis has been induced in highresponder strains of rats with CII purified from the cartilage of a number of species-e.g., human, chick, bovine, porcine, rabbit, guinea pig, and deer. With the unique exception of the DA rat (Griffiths et al, 1993), most strains respond poorly to rat CII compared to other mammalian and avian products (Griffiths et al, 1992;Cremer et al, 1994). Arthritic responses to chick and bovine CII are often equivalent, with the notable exception of ACI and BN rats where disparate responses are seen.…”