Microbiology & Immunology Publications
The Relationship between Predicted Peptide-MHC Class II Affinity and T-cell Activation in a HLA-DRbeta1*0401 Transgenic Mouse Model
Document Type
Article
Publication Date
11-4-2002
Journal
Arthritis Research and Therapy
Volume
5
Issue
1
First Page
R40
Last Page
R48
Abstract
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-gamma) 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.
Notes
Published in: Arthritis Res Ther, 2003, 5:R40-R48. doi: 10.1186/ar605