LYMPHOCYTE-RESPONSES TO DR1 4 RESTRICTED PEPTIDES IN RHEUMATOID-ARTHRITIS/

Objective-To determine whether analog and unrelated DR1/4 binding pept ides alter DR1/4 restricted responses of peripheral blood lymphocytes (PBL) from patients with rheumatoid arthritis (RA). Methods-PBL from 2 5 patients with RA and 12 healthy controls were cultured with DR1/4 re stricted peptides of the influenza haemagglutinin, amino acids 307-319 (HA) and matrix proteins, amino acids 17-29 (IM). Responses were dete rmined by H-3-thymidine uptake proliferation assays and limiting dilut ion analysis. Competitor peptides were analogs HA-R(312) and HA-K-313 differing from HA by one amino acid at the 312 or 313 position respect ively or unrelated peptides which bind to DR1/4. Results-The responses of eight patients with RA to the two stimulatory influenza peptides d id not differ significantly from controls and this was confirmed by th e frequency estimate of T cells in PBL which responded to HA (mean fre quency: 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 H A peptide inhibited HA specific peptide responses of PBL from patients with RA and controls. Inhibition was also detected with unrelated pep tides which bind to DR1/4 but to which the individual did not respond. Conclusion-Similar responses to two DR1/4 restricted peptides were ob served in patients with RA and controls. Both antigen analog- and unre lated peptide-major histocompatibility complexes (MHC) can result in t he inhibition of antigen specific responses in multiclonal human lymph ocyte populations. However, an analog peptide may be stimulatory in so me individuals. These results provide some initial data for the develo pment of a rational approach to MHC-specific immunomodulation rheumato id arthritis.