The relationship between predicted peptide–MHC class II affinity and T-cell activation in a HLA-DRβ1*0401 transgenic mouse model

Arthritis Research & Therapy

Jonathan A Hill³  Dequn Wang⁴  Anthony M Jevnikar²  Ewa Cairns¹  David A Bell¹ 

[1] EC and DAB are considered co-senior authors of this work

[2] Division of Nephrology, London Health Sciences Center, London, Ontario, Canada

[3] Department of Microbiology and Immunology, University of Western Ontario, London, Canada

[4] Current address: Applied Biotech Inc., San Diego, California, USA

关键词: T cell;    rheumatoid arthritis;    peptide;    MHC class II;    cross-reactivity;   

Others  :  1101411
DOI  :  10.1186/ar605

 received in 2002-03-27, accepted in 2002-10-04,  发布年份 2002

【 摘 要 】

The HLA-DRB1*0401 MHC class II molecule (DR4) is genetically associated with rheumatoid arthritis. It has been proposed that this MHC class II molecule participates in disease pathogenesis by presenting arthritogenic endogenous or exogenous peptides to CD4⁺ T cells, leading to their activation and resulting in an inflammatory response within the synovium. In order to better understand DR4 restricted T cell activation, we analyzed the candidate arthritogenic antigens type II collagen, human aggrecan, and the hepatitis B surface antigen for T-cell epitopes using a predictive model for determining peptide–DR4 affinity. We also applied this model to determine whether cross-reactive T-cell epitopes can be predicted based on known MHC–peptide–TCR interactions. Using the HLA-DR4-IE transgenic mouse, we showed that both T-cell proliferation and Th1 cytokine production (IFN-γ) correlate with the predicted affinity of a peptide for DR4. In addition, we provide evidence that TCR recognition of a peptide–DR4 complex is highly specific in that similar antigenic peptide sequences, containing identical amino acids at TCR contact positions, do not activate the same population of T cells.

【 授权许可】

   
2003 Hill et al., licensee BioMed Central Ltd. This is an Open Access article: Media for any non-commercial purpose, provided this notice is presented along with the articles original URL.

【 图 表 】

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