Influenza virus haemagglutinin-derived peptides inhibit T-cell activation induced by HLA-DR4/1 specific peptides in rheumatoid arthritis.
OBJECTIVE
To investigate whether influenza virus haemagglutinin (HA)-derived altered peptide ligands (APLs) could abrogate T-cell responses to wild type HA308-317 or type II collagen (CII) 263-272 peptides and explore the potential inhibitory effects of the altered HA308-317 peptides on T-cell activation in rheumatoid arthritis (RA).


METHODS
Altered HA308-317 peptides containing substitutions of T-cell receptor (TCR)-contact residues were synthesized. Peripheral blood mononuclear cells (PBMC) were obtained from 27 HLA-DR4/1-positive RA patients. Impact of the altered HA308-317 peptides on T-cell responses and the inhibitory effects on T-cell activation were determined by using PBMC from RA.


RESULTS
The results showed that the altered HA308-317 peptides could bind to HLA-DR4/1 on cell surface and had no effects on T-cell proliferation and CD25 expression. Moreover, all the altered HA308-317 peptides inhibited T-cell proliferative responses to wild type HA308-317 or CII263-272. In addition, Th1 type cytokine profile was found when PBMC were cultured with wild type HA308-317 or CII263-272, but not the altered HA 308-317 peptides.


CONCLUSIONS
It is suggested that altered HA308-317 peptides bind to the RA-associated HLA-DR4/1 with no stimulating effects on T cells and might be potentially important in inhibition of T-cell activation in RA.
Li
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Department of Rheumatology and Immunology, People's Hospital, Beijing University, Beijing, China.
Li
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D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D015798:HLA-DR1 Antigen / Q000378:metabolism*; D015804:HLA-DR4 Antigen / Q000378:metabolism*; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000494:pharmacology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000276:immunology*
D015798:HLA-DR1 Antigen; D015804:HLA-DR4 Antigen; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D010446:Peptide Fragments