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一种可溶性二价I类主要组织相容性复合体/免疫球蛋白G1融合蛋白在体内激活CD8 + T细胞。

A soluble divalent class I MHC/IgG1 fusion protein activates CD8+ T cells in vivo.

作者信息

Carey Brenna, DeLay Monica, Strasser Jane E, Chalk Claudia, Dudley-McClain Kristen, Milligan Gregg N, Brunner Hermine I, Thornton Sherry, Hirsch Raphael

机构信息

William S. Rowe Division of Rheumatology, Children's Hospital Medical Center, Cincinnati, OH 45229, USA.

出版信息

Clin Immunol. 2005 Jul;116(1):65-76. doi: 10.1016/j.clim.2005.02.013.

DOI:10.1016/j.clim.2005.02.013
PMID:15925833
Abstract

CD8+ T lymphocytes recognize tumor and viral antigens bound to class I major histocompatibility complexes (MHC). Tumors and viruses may evade detection by preventing antigen presentation. The present study was designed to determine whether a soluble divalent fusion protein, containing the extracellular domains of a class I MHC molecule fused to beta2-microglobulin and the constant domains of IgG1, could induce an immune response in vivo. Administration to mice of the fusion protein loaded with a tumor peptide induced peptide-specific T cell activation and retarded tumor growth. Administration of the fusion protein loaded with a glycoprotein B (gB) peptide derived from herpes simplex virus type 1 (HSV-1) induced gB-specific cytotoxic T lymphocytes and protected mice from a lethal HSV-1 challenge. These data suggest that antigen-loaded MHC/IgG fusion proteins may enhance T cell immunity in conditions where antigen presentation is altered.

摘要

CD8 + T淋巴细胞识别与I类主要组织相容性复合体(MHC)结合的肿瘤和病毒抗原。肿瘤和病毒可能通过阻止抗原呈递来逃避检测。本研究旨在确定一种可溶性二价融合蛋白,其包含与β2-微球蛋白融合的I类MHC分子的细胞外结构域和IgG1的恒定结构域,是否能在体内诱导免疫反应。给小鼠注射负载肿瘤肽的融合蛋白可诱导肽特异性T细胞活化并延缓肿瘤生长。给小鼠注射负载源自单纯疱疹病毒1型(HSV-1)的糖蛋白B(gB)肽的融合蛋白可诱导gB特异性细胞毒性T淋巴细胞,并保护小鼠免受致死性HSV-1攻击。这些数据表明,在抗原呈递改变的情况下,负载抗原的MHC / IgG融合蛋白可能增强T细胞免疫。

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