Altered collagen II peptides inhibited T-cell activation in rheumatoid arthritis.
It has been reported that collagen II (CII)-derived peptide induced T-cell activation via its amino acids responsible for T-cell receptor (TCR) recognition. In this study, three altered CII263-272 peptide ligands (APL) containing multiple substitutions of TCR contact residues were synthesized. Their roles in inhibition of T-cell activation were evaluated in peripheral blood lymphocytes (PBL) of rheumatoid arthritis (RA) in vitro. It was shown that 41% (25/61) of RA patients were responsive to the wild-type antigenic CII263-272. In contrast, marginal or silent T-cell responses to the three APLs were found, accompanied by inhibitory effects on secretion of Th1 type cytokines and expression of cell surface markers, CD69 and CD25. In addition, T-cell activation induced by the wild-type antigenic CII263-272 was inhibited by all the three APLs in a dose-dependent manner. It is demonstrated that APLs with substitutions of TCR contact residues are capable of down-regulating T-cell responses in PBLs of RA, suggesting that the CII-derived APLs are potentially therapeutic in RA.
Li
Ru
R
Department of Rheumatology and Immunology, People's Hospital, Beijing University Medical School, 11 Xizhimen South St., Beijing 100044, China.
Li
Xia
X
Li
Zhanguo
Z
D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis / Q000235:genetics; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D024043:Collagen Type II / Q000276:immunology* / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D005260:Female; D015804:HLA-DR4 Antigen / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D037181:Lectins, C-Type; D008024:Ligands; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000276:immunology* / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D024043:Collagen Type II; D016207:Cytokines; D015804:HLA-DR4 Antigen; D007166:Immunosuppressive Agents; D037181:Lectins, C-Type; D008024:Ligands; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell; D015375:Receptors, Interleukin-2; D000099192:CD69 Antigens