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CD 74/ DQA 1 dimers predispose to the development of arthritis in humanized mice
Author(s) -
David Luckey,
Gokhale Ameya,
Jois Seetharama,
Johnson Aaron,
Behrens Marshall,
Luthra Harvinder,
Taneja Veena
Publication year - 2016
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.12551
Subject(s) - arthritis , rheumatoid arthritis , immunology , antigen , dimer , medicine , chemistry , organic chemistry
Summary Rheumatoid arthritis ( RA ) is associated with the presence of certain HLA class II genes. However, why some individuals carrying RA non‐associated alleles develop arthritis is still unexplained. The trans‐heterodimer between two RA non‐associated HLA genes can render susceptibility to develop arthritis in humanized mice, DQA 1*0103/ DQB 1*0604 , suggesting a role for DQ α chains in pathogenesis. In this study we determined the role of DQA 1 in arthritis by using mice expressing DQA 1*0103 and lacking endogenous class II molecules. Proximity ligation assay showed that DQA 1*0103 is expressed on the cell surface as a dimer with CD 74. Upon immunization with type II collagen, DQA 1*0103 mice generated an antigen‐specific cellular and humoral response and developed severe arthritis. Structural modelling suggests that DQA 1*0103 / CD 74 form a pocket with similarity to the antigen binding pocket. DQA 1*0103 mice present type II collagen‐derived peptides that are not presented by an arthritis‐resistant DQA 1*0103/ DQB 1*0601 allele, suggesting that the DQA 1*0103 / CD 74 dimer may result in presentation of unique antigens and susceptibility to develop arthritis. The present data provide a possible explanation by which the DQA 1 molecule contributes to susceptibility to develop arthritis.