Peptides presented by DR4/1 may be involved in the pathogenesis of rheumatoid arthritis (RA). T cell responses to DR4/1-restricted peptides unrelated to the causative antigen may be altered in RA. Thus, DR4/1-restricted lymphocyte responses in healthy volunteers and patients with RA were determined.
Peripheral blood lymphocytes (PBL) and synovial lymphocytes were cultured with synthetic peptides spanning the 19-kd Mycobacterium tuberculosis (MT) protein.
3H-thymidine uptake by PBL from 5 of 7 healthy individuals and 5 of 7 RA patients increased in response to the N-terminal peptide (residues 1-20). Eleven fresh synovial fluid and 4 fresh synovial tissue (ST) lymphocyte samples did not proliferate in response to any of the peptides. However, the same T cell epitope was identified by ST lymphocytes when these were precultured. The N-terminal peptide was not a common antibody-binding site, unlike several of the other peptides.
Similar responses by RA and normal PBL to a DR4/1-restricted immunodominant T cell epitope on the 19-kd MT protein were observed. The responses were more readily detected in PBL than in synovial lymphocytes. These observations may be relevant for assessing unrelated synthetic peptides in the development of DR4/1-restricted peptide immunotherapy.