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靶向猪唾液酸粘附素受体可改善抗原向T细胞的呈递。

Targeting to porcine sialoadhesin receptor improves antigen presentation to T cells.

作者信息

Revilla Concepción, Poderoso Teresa, Martínez Paloma, Alvarez Belén, López-Fuertes Laura, Alonso Fernando, Ezquerra Angel, Domínguez Javier

机构信息

Dpto. Biotecnología, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), 28040, Madrid, Spain.

出版信息

Vet Res. 2009 May-Jun;40(3):14. doi: 10.1051/vetres:2008052. Epub 2008 Dec 12.

Abstract

Antibody-mediated targeting of antigen to specific antigen presenting cells (APC) receptors is an attractive strategy to enhance T cell immune responses to weak immunogenic antigens. Here, we describe the characterization of two monoclonal antibodies (mAb) against different epitopes of porcine sialoadhesin (Sn) and evaluate in vitro the potential of targeting this receptor for delivery of antigens to APC for T cell stimulation. The specificity of these mAb was determined by amino acid sequence analysis of peptides derived from the affinity purified antigen. Porcine Sn is expressed by macrophages present in the border between white and red pulp of the spleen and in the subcapsular sinus of lymph nodes, an appropriate location for trapping blood and lymph-borne antigens. It is also expressed by alveolar macrophages and monocyte-derived dendritic cells (MoDC). Blood monocytes are negative for this molecule, but its expression can be induced by treatment with IFN-alpha. MAb bound to Sn is rapidly endocytosed. MAb to sialoadhesin induced in vitro T cell proliferation at concentrations 100-fold lower than the non-targeting control mAb when using T lymphocytes from pigs immunized with mouse immunoglobulins as responder cells and IFN-alpha treated monocytes or MoDC as APC, suggesting a role of sialoadhesin in antigen uptake and/or delivery into the presentation pathway in APC.

摘要

抗体介导的将抗原靶向特定抗原呈递细胞(APC)受体是增强T细胞对弱免疫原性抗原免疫反应的一种有吸引力的策略。在此,我们描述了针对猪唾液酸黏附素(Sn)不同表位的两种单克隆抗体(mAb)的特性,并在体外评估了靶向该受体将抗原递送至APC以刺激T细胞的潜力。这些mAb的特异性通过对亲和纯化抗原衍生肽段的氨基酸序列分析来确定。猪Sn由存在于脾脏白髓和红髓交界处以及淋巴结被膜下窦中的巨噬细胞表达,这是捕获血液和淋巴源性抗原的合适位置。它也由肺泡巨噬细胞和单核细胞衍生的树突状细胞(MoDC)表达。血液单核细胞对此分子呈阴性,但用IFN-α处理可诱导其表达。与Sn结合的mAb可迅速被内吞。当使用用小鼠免疫球蛋白免疫的猪的T淋巴细胞作为反应细胞,并用IFN-α处理的单核细胞或MoDC作为APC时,针对唾液酸黏附素的mAb在比非靶向对照mAb低100倍的浓度下即可诱导体外T细胞增殖,这表明唾液酸黏附素在APC的抗原摄取和/或递送至呈递途径中发挥作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d606/2695033/7e6cf457e89f/vetres-40-14-fig1.jpg

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