每年出版 6 期
ISSN 打印: 1040-8401
ISSN 在线: 2162-6472
Indexed in
PART III. Autoimmunity
An Altered Peptide Ligand of Type II Collagen Suppresses Autoimmune Arthritis
摘要
On the basis of the hypothesis that immunity to type II collagen (CII) contributes to joint inflammation, our goal is to develop an immunotherapy capable of selectively blocking immunity to a particular autoantigen without interfering with the beneficial functions of the immune system. CII is the major protein component of articular cartilage and autoimmunity to CII is strongly associated with rheumatoid arthritis in man. Our laboratory has previously identified a region of type II collagen (CII), CII245−270 that contains a prominent T-cell epitope in the immune response to CII. Residues critical to the I-Aq-restricted presentation of this determinant have been characterized. When synthetic analog peptides were developed that contain site-directed substitutions in critical positions, we found that that CII245−270 (A260, B261, N263) (A9), profoundly suppressed collagen-induced arthritis. When DBA/1 mice were coimmunized with CII and the analog peptide, the incidence and severity of arthritis was greatly reduced concordant with the humoral immune responses to CII. Moreover, the suppression could be transferred with A9-immune spleen cells and was accompanied by a Th2-type cytokine profile. When we compared T-cell signals in response to A9 to those of wild-type (WT) peptide, we found that APCs prepulsed with WT peptide induced strong phosphorylation of both TCR ζ chain and Zap-70, while A9 did not. Since T cells clearly respond to A9 with cytokine secretion, we hypothesize that A9 induces an alternate signaling pathway and we speculate that this pathway involves phosphorylation of Syk, a kinase ordinarily utilized by B cells. Activation of this alternative pathway is a novel observation and may represent an important means by which the phenotype of the responding T cell is altered. Elucidation of the mechanism by which A9 prevents arthritis may lead to development of novel immunotherapeutic approaches to antigen specific treatment of autoimmunity.
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Czaja Albert J., Emerging Opportunities for Site-Specific Molecular and Cellular Interventions in Autoimmune Hepatitis, Digestive Diseases and Sciences, 55, 10, 2010. Crossref
-
Myers Linda K., Cullins David L., Park Jeoung-Eun, Yi Ae-Kyung, Brand David D., Rosloniec Edward F., Stuart John M., Kang Andrew H., Peptide ligand structure and I-Aq binding avidity influence T cell signaling pathway utilization, Clinical Immunology, 160, 2, 2015. Crossref
-
Katsara Maria, Minigo Gabriela, Plebanski Magdalena, Apostolopoulos Vasso, The good, the bad and the ugly: how altered peptide ligands modulate immunity, Expert Opinion on Biological Therapy, 8, 12, 2008. Crossref
-
Braun Ruedi K., Martin Alicia, Shah Shivanee, Iwashima Makio, Medina Melissa, Byrne Kathryn, Sethupathi Periannan, Wigfield Christopher H., Brand David D., Love Robert B., Inhibition of bleomycin-induced pulmonary fibrosis through pre-treatment with collagen type V, The Journal of Heart and Lung Transplantation, 29, 8, 2010. Crossref
-
Jensen Kirk D.C., Sercarz Eli E., Gabaglia Claudia Raja, Altered peptide ligands can modify the Th2 T cell response to the immunodominant 161-175 peptide of LACK (Leishmania homolog for the receptor of activated C kinase), Molecular Immunology, 46, 3, 2009. Crossref
-
Myers Linda K., Cullins David L., Brand David D., Kleinau Sandra, Stuart John M., Kang Andrew H., T cells stimulated with an analog peptide of type II collagen require the Fc receptor γ-chain to secrete interleukin-4 and suppress autoimmune arthritis in mice, Arthritis & Rheumatism, 63, 9, 2011. Crossref
-
Park Jeoung-Eun, Rotondo Jeffrey A., Cullins David L., Brand David D., Yi Ae-Kyung, Stuart John M., Kang Andrew H., Myers Linda K., Characterization of the Syk-Dependent T Cell Signaling Response to an Altered Peptide, The Journal of Immunology, 197, 12, 2016. Crossref
-
Dai Meilu, Liu Xin, Wang Nanping, Sun Jiao, Squid type II collagen as a novel biomaterial: Isolation, characterization, immunogenicity and relieving effect on degenerative osteoarthritis via inhibiting STAT1 signaling in pro-inflammatory macrophages, Materials Science and Engineering: C, 89, 2018. Crossref
-
Park Jeoung-Eun, Majumdar Sirshendu, Brand David D., Rosloniec Edward F., Yi Ae-Kyung, Stuart John M., Kang Andrew H., Myers Linda K., The role of Syk in peripheral T cells, Clinical Immunology, 192, 2018. Crossref
-
Xu Xiao, Sui Baiyan, Liu Xin, Sun Jiao, Superior low-immunogenicity of tilapia type I collagen based on unique secondary structure with single calcium binding motif over terrestrial mammals by inhibiting activation of DC intracellular Ca2+-mediated STIM1-Orai1/NF-кB pathway, Materials Science and Engineering: C, 131, 2021. Crossref
-
De Santis M, Ceribelli A, Cavaciocchi F, Generali E, Massarotti M, Isailovic N, Crotti C, Scherer H U, Montecucco C, Selmi C, Effects of type II collagen epitope carbamylation and citrullination in human leucocyte antigen (HLA)-DR4+ monozygotic twins discordant for rheumatoid arthritis, Clinical and Experimental Immunology, 185, 3, 2016. Crossref
-
Park Jeoung-Eun, Cullins David, Zalduondo Lillian, Barnett Stacey L., Yi Ae-Kyung, Kleinau Sandra, Stuart John M., Kang Andrew H., Myers Linda K., Molecular Basis for T Cell Response Induced by Altered Peptide Ligand of Type II Collagen, Journal of Biological Chemistry, 287, 23, 2012. Crossref
-
Liu Zhenming, Li Bo, Li Xia, Zhang Liangren, Lai Luhua, Identification of Small-Molecule Inhibitors against Human Leukocyte Antigen-Death Receptor 4 (HLA-DR4) Through a Comprehensive Strategy, Journal of Chemical Information and Modeling, 51, 2, 2011. Crossref
-
Wenhart Clara, Holthoff Hans-Peter, Reimann Andreas, Li Zhongmin, Faßbender Julia, Ungerer Martin, A fructosylated peptide derived from a collagen II T cell epitope for long-term treatment of arthritis (FIA-CIA) in mice, Scientific Reports, 11, 1, 2021. Crossref
-
Page Audrey, Fusil Floriane, Cosset François-Loïc, Antigen-specific tolerance approach for rheumatoid arthritis: Past, present and future, Joint Bone Spine, 88, 4, 2021. Crossref