Lymphocyte responses to DR1/4 restricted peptides in rheumatoid arthritis.

Abstract

To determine whether analog and unrelated DR1/4 binding peptides alter DR1/4 restricted responses of peripheral blood lymphocytes (PBL) from patients with rheumatoid arthritis (RA). PBL from 25 patients with RA and 12 healthy controls were cultured with DR1/4 restricted peptides of the influenza haemagglutinin, amino acids 307-319 (HA) and matrix proteins, amino acids 17-29 (IM). Responses were determined by 3H-thymidine uptake proliferation assays and limiting dilution analysis. Competitor peptides were analogs HA-R312 and HA-K313 differing from HA by one amino acid at the 312 or 313 position respectively or unrelated peptides which bind to DR1/4. The responses of eight patients with RA to the two stimulatory influenza peptides did not differ significantly from controls and this was confirmed by the frequency estimate of T cells in PBL which responded to HA (mean frequency: 1 in 9.0 x 10(4), n = 5, in DR1/4+ RA patients, 1 in 7.6 x 10(4), n = 5, in DR1/4+ healthy controls). DR1/4 binding analogs of the HA peptide inhibited HA specific peptide responses of PBL from patients with RA and controls. Inhibition was also detected with unrelated peptides which bind to DR1/4 but to which the individual did not respond. Similar responses to two DR1/4 restricted peptides were observed in patients with RA and controls. Both antigen analog- and unrelated peptide-major histocompatibility complexes (MHC) can result in the inhibition of antigen specific responses in multi-clonal human lymphocyte populations. However, an analog peptide may be stimulatory in some individuals. These results provide some initial data for the development of a rational approach to MHC-specific immunomodulation in rheumatoid arthritis.