Polymorphism of the MHC class IIEbgene determines the protection against collagen-induced arthritis

摘要

Collagen-induced arthritis (CIA) is an animal model of auto immune polyarthritis, sharing similarities with rheumatoid arthritis (RA). Paradoxally, susceptibility to mouse CIA is controlled by theH2Aloci (DQhomologous) while RA is linked toHLA.DRgenes (H2Ehomologous). We recently showed that the Eβdmolecule prevents CIA development in susceptibleH2qmice. We addressed the question of whetherH2Ebpolymorphism will influence CIA incidence asHLA.DRB1polymorphism does in RA. In F1mice, only H2Ebdand H2Ebsmolecules showed protection. Using recombinant B10.RDD (Ebd/b) mice, we found that CIA protection was mediated by the first domain of the Eβdmolecule. Using peptides covering the third hypervariable region of the Eβ chain, we found a perfect correlation between presentation of Eβ peptides by the H2Aqmolecule and protection on CIA. Therefore, the mechanism by whichH2Ebprotects against CIA seems to rely on the affinity of Eβ peptides for the H2Aqmole