Peptide competition at the level of MHC-binding sites using T cell clones from a rheumatoid arthritis patient

The inhibition of antigen presentation in rheumatoid arthritis by blocking peptide binding to MHC at the antigen presenting cell (APC) level was investigated using various synthetic peptides derived from the 65 kDa mycobacterial protein. Human T cell clones from tuberculosis and rheumatoid arthritis patients were stimulated with peptides in the presence of irradiated APCs (autologous or DR homozygous EBV-B cell lines). Two peptides (residues 65-85 and 412-426) were found to be able to bind to the HLA-DR1 protein. Cross-competition was observed between these peptides when APCs were cultured with a suboptimal concentration of stimulator peptide in the presence of various concentrations of competitor peptides and T cell clones from tuberculosis patients as responder cells. These T cell clones responded not only to the peptides but also to the native protein. In other experiments, we used T cell clones from a rheumatoid arthritis patient to demonstrate the blocking of MHC-binding sites by adding the p412-426 in the recognition of DR1 restricted T cell clone specific to p65-85; MHC binding was not observed using a control peptide (residues 198-217). This approach has permitted the identification of MHC-specific blockers. Further experimentation is required to determine the particular amino acids involved in MHC binding. Our data support the idea that modulation of antigen presentation by peptide competition could be a useful tool for immunotherapy in autoimmune diseases.