OR11 Comparison of arthritogenic peptide binding to DRB101:01 and DRB101:02

• Published in: Human immunology 2015-10, Vol.76, p.22-22
• Main Authors: Roark, Christina L, Anderson, Kirsten M, Aubrey, Michael T, Rosloniec, Edward F, Freed, Brian M
• Format: Article
• Language: English
• Subjects: Allergy and Immunology
• ISSN: 0198-8859; 1879-1166
• DOI: 10.1016/j.humimm.2015.07.031

Aim Susceptibility to rheumatoid arthritis (RA) has been shown to be associated with DRB1*04 and *01 alleles due to the presence of the QRRAA “shared epitope” in amino acids 70–74. However, despite both DRB1*01:01 and *01:02 having the QRRAA shared epitope, DRB1*01:01 is more strongly associated with RA. The purpose of this study was to determine if the binding of citrullinated and non-citrullinated peptides to DRB1*01:01, *01:02 and *01:03 (as a negative control) could be used to dissect the role of the shared epitope and other amino acids in RA susceptibility. Methods Binding of type II collagen259–273 (CII), citrullinated and native vimentin66–78 , and citrullinated and native α -enolase11–25 was measured on cell lines expressing DRB1*01:01, *01:02 and *01:03 by flow cytometry. Single site mutagenesis was performed to examine how the differences between these alleles affect peptide binding and T cell responses. Results DRB1*01:01 exhibited an 8.2-fold preference for binding citrullinated vimentin66–78 over its native form, compared to 7.8-fold for *01:02 and 0.68-fold (preference for binding native) for *01:03. DRB1*01:01 also exhibited a 2-fold preference for binding citrullinated α -enolase11–25 over native, compared to 1.0-fold (no preference) for *01:02 and 0.49-fold (preference for native) for *01:03. In addition, DRB1*01:01 bound more type II collagen (CII)259–273 (3.7-fold over background) than *01:02 (1.1-fold) and *01:03 (1.7-fold). Mutating G86 in DRB1*01:01 to the residue found in DRB1*01:02 (V86) abolished citrullinated α -enolase11–25 and CII259–273 binding and decreased citrullinated vimentin66–78 binding (1.7-fold). Conclusion The difference in susceptibility between DRB1*01:01 and *01:02 for RA may be explained by the effect of position 86 on peptide binding.