Lymphocyte responses to DR4/1-restricted peptides in rheumatoid arthritis. The immunodominant T cell epitope on the 19-kd Mycobacterium tuberculosis protein.
OBJECTIVE
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.


METHODS
Peripheral blood lymphocytes (PBL) and synovial lymphocytes were cultured with synthetic peptides spanning the 19-kd Mycobacterium tuberculosis (MT) protein.


RESULTS
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.


CONCLUSIONS
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.
Tan
P L
PL
Department of Molecular Medicine, University of Auckland School of Medicine, New Zealand.
Farmiloe
S
S
Young
J
J
Watson
J D
JD
Skinner
M A
MA
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001172:Arthritis, Rheumatoid / Q000209:etiology / Q000276:immunology*; D001426:Bacterial Proteins / Q000032:analysis / Q000378:metabolism / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D005260:Female; D015798:HLA-DR1 Antigen / Q000032:analysis* / Q000276:immunology; D015804:HLA-DR4 Antigen / Q000032:analysis* / Q000276:immunology; D006801:Humans; D016056:Immunodominant Epitopes / Q000032:analysis / Q000276:immunology / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000737:chemistry*; D013583:Synovial Membrane / Q000473:pathology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D013936:Thymidine / Q000378:metabolism; D014316:Tritium
D001426:Bacterial Proteins; D015798:HLA-DR1 Antigen; D015804:HLA-DR4 Antigen; D016056:Immunodominant Epitopes; D014316:Tritium; D004247:DNA; D013936:Thymidine