The inhibitory effect of altered collagen II peptide on HLA-DRB1-restricted T-cell activation.
It has been known that rheumatoid arthritis (RA)-associated antigenic peptides CII263-272 are coupled with human leucocyte antigen (HLA)-DRB1 and recognized by T-cell receptor (TCR), which in turn induced T-cell proliferation and pathogenesis of RA. Non-T-cell-stimulating type II collagen (CII) peptides might be generated by removing the amino acids responsible for TCR contact and keeping the HLA-DR-binding residues intact. In this study, a panel of altered CII peptides (APs) with consecutive or single substitutions of the TCR-contacting residues were synthesized. Through peptide binding and T-cell activation assays, we demonstrated that altered CII263-272 peptides with substitution of the TCR-contacting residues did not or barely induced T-cell activation; one of the best non-T-cell-stimulating peptide AP268-270 inhibited the binding of wild-type CII263-272 to HLA-DR1 and T-cell activation triggered by wild-type CII263-272 and HA306-318 in a dose-response manner. These data suggest that removal of the TCR-contacting residues of CII263-272 leads to HLA-DRB1 binding and low T-cell-stimulating peptides, which could potentially inhibit the T-cell response induced by HLA-DRB1-binding antigenic peptides.
Cheng
Y J
YJ
Department of Rheumatology & Immunology, People's Hospital, Peking University Medical School, Beijing, China.
Zhou
Q
Q
Li
Z G
ZG
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000276:immunology; D002460:Cell Line; D024043:Collagen Type II / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D006684:HLA-DR Antigens / Q000378:metabolism*; D059811:HLA-DRB1 Chains; D006801:Humans; D007739:L Cells; D008213:Lymphocyte Activation; D051379:Mice; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*; D014162:Transfection
D024043:Collagen Type II; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell