title: Chaperonin-containing T-complex Protein 1 Subunit ζ Serves as an Autoantigen Recognized by Human Vδ2 γδ T Cells in Autoimmune Diseases.
abstract: Human γδ T cells recognize conserved endogenous and stress-induced antigens typically associated with autoimmune diseases. However, the role of γδ T cells in autoimmune diseases is not clear. Few autoimmune disease-related antigens recognized by T cell receptor (TCR) γδ have been defined. In this study, we compared Vδ2 TCR complementarity-determining region 3 (CDR3) between systemic lupus erythematosus (SLE) patients and healthy donors. Results show that CDR3 length distribution differed significantly and displayed oligoclonal characteristics in SLE patients when compared with healthy donors. We found no difference in the frequency of Jδ gene fragment usage between these two groups. According to the dominant CDR3δ sequences in SLE patients, synthesized SL2 peptides specifically bound to human renal proximal tubular epithelial cell line HK-2; SL2-Vm, a mutant V sequence of SL2, did not bind. We identified the putative protein ligand chaperonin-containing T-complex protein 1 subunit ζ (CCT6A) using SL2 as a probe in HK-2 cell protein extracts by affinity chromatography and liquid chromatography-electrospray ionization-tandem mass spectrometry analysis. We found CCT6A expression on the surface of HK-2 cells. Cytotoxicity of only Vδ2 γδ T cells to HK-2 cells was blocked by anti-CCT6A antibody. Finally, we note that CCT6A concentration was significantly increased in plasma of SLE and rheumatoid arthritis patients. These data suggest that CCT6A is a novel autoantigen recognized by Vδ2 γδ T cells, which deepens our understanding of mechanisms in autoimmune diseases.
authors.affiliation: From the Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, State Key Laboratory of Medical Molecular Biology, Beijing 100005, China and.
authors.forename: Hui
authors.initials: H
authors.lastname: Chen
authors.affiliation: From the Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, State Key Laboratory of Medical Molecular Biology, Beijing 100005, China and.
authors.forename: Hongqin
authors.initials: H
authors.lastname: You
authors.affiliation: From the Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, State Key Laboratory of Medical Molecular Biology, Beijing 100005, China and.
authors.forename: Lifang
authors.initials: L
authors.lastname: Wang
authors.affiliation: the Department of Rheumatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100730, China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Zhang
authors.affiliation: From the Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, State Key Laboratory of Medical Molecular Biology, Beijing 100005, China and jzhang42@163.com.
authors.forename: Jianmin
authors.initials: J
authors.lastname: Zhang
authors.affiliation: From the Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, State Key Laboratory of Medical Molecular Biology, Beijing 100005, China and hewei@ngd.org.cn.
authors.forename: Wei
authors.initials: W
authors.lastname: He
mesh_terms: D000328:Adult; D000368:Aged; D001324:Autoantigens / Q000235:genetics / Q000276:immunology*; D002460:Cell Line; D056404:Chaperonin Containing TCP-1 / Q000235:genetics / Q000276:immunology*; D022801:Complementarity Determining Regions / Q000235:genetics / Q000276:immunology*; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics / Q000276:immunology*
chemical_list: D001324:Autoantigens; C533302:CCT6A protein, human; D022801:Complementarity Determining Regions; D016692:Receptors, Antigen, T-Cell, gamma-delta; D056404:Chaperonin Containing TCP-1
keywords: CCT6A; CDR3δ; T cell receptor (TCR); antigen; autoantigen; autoimmune disease; autoimmune diseases; cellular immune response; chaperonin-containing T-complex protein 1 subunit zeta; complementarity-determining region 3 delta; gamma delta T cells; immunology