Báo cáo y học: Antigenized antibodies expressing Vβ8.2 TCR peptides immunize against rat experimental allergic encephalomyelitis

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Báo cáo y học: "Antigenized antibodies expressing Vβ8.2 TCR peptides immunize against rat experimental allergic encephalomyelitis"Journal of Immune Based Therapiesand Vaccines BioMed Central Open AccessOriginal researchAntigenized antibodies expressing Vβ8.2 TCR peptides immunizeagainst rat experimental allergic encephalomyelitisCristina Musselli, Svetlana Daverio-Zanetti and Maurizio Zanetti*Address: The Department of Medicine and Cancer Center, University of California, San Diego, La Jolla CA USAEmail: Cristina Musselli - zanettofc@ucsd.edu; Svetlana Daverio-Zanetti - szanetti@san.rr.com; Maurizio Zanetti* - mzanetti@ucsd.edu* Corresponding authorPublished: 12 November 2004 Received: 24 June 2004 Accepted: 12 November 2004Journal of Immune Based Therapies and Vaccines 2004, 2:9 doi:10.1186/1476-8518-2-9This article is available from: http://www.jibtherapies.com/content/2/1/9© 2004 Musselli et al; licensee BioMed Central Ltd.This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0),which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.EAETCRIdiotypeRegulation Abstract Background: Immunity against the T cell receptor (TCR) is considered to play a central role in the regulation of experimental allergic encephalomyelitis (EAE), a model system of autoimmune disease characterized by a restricted usage of TCR genes. Methods of specific vaccination against the TCR of pathogenetic T cells have included attenuated T cells and synthetic peptides from the sequence of the TCR. These approaches have led to the concept that anti-idiotypic immunity against antigenic sites of the TCR, which are a key regulatory element in this disease. Methods: The present study in the Lewis rat used a conventional idiotypic immunization based on antigenized antibodies expressing selected peptide sequences of the Vβ8.2 TCR (93ASSDSSNTE101 and 39DMGHGLRLIHYSYDVNSTEKG59). Results: The study demonstrates that vaccination with antigenized antibodies markedly attenuates, and in some instances, prevents clinical EAE induced with the encephalitogenic peptide 68GSLPQKSQRSQDENPVVHF88 in complete Freunds adjuvant (CFA). Antigenized antibodies induced an anti-idiotypic response against the Vβ8.2 TCR, which was detected by ELISA and flowcytometry. No evidence was obtained of a T cell response against the corresponding Vβ8.2 TCR peptides. Conclusions: The results indicate that antigenized antibodies expressing conformationally- constrained TCR peptides are a simple means to induce humoral anti-idiotypic immunity against the TCR and to vaccinate against EAE. The study also suggests the possibility to target idiotypic determinants of TCR borne on pathogenetic T cells to vaccinate against disease. peptides from the MBP sequence [1]. EAE can also be ini-IntroductionExperimental allergic encephalomyelitis (EAE) is an tiated by the passive transfer of encephalitogenic, MBP-experimentally induced autoimmune disease mediated by specific T cell lines or clones [2,3]. In the Lewis rat, EAE isT cells. It can be induced in susceptible animals either by characterized by a self limiting, ascending, hind limbimmunization with myelin basic protein (MBP) or prote- paralysis. Histologically, EAE is hallmarked by perivascu-olipid protein PLP, or by immunization with synthetic lar and submeningeal infiltration of inflammatory cells Page 1 of 12 (page number not for citation purposes)Journal of Immune Based Therapies and Vaccines 2004, 2:9 http://www.jibtherapies.com/content/2/1/9within the brain and spinal cord [4]. After recovery, ani- ...