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

Targeting to porcine sialoadhesin receptor improves antigen presentation to T cells.
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DOI:
10.1051/vetres:2008052
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发表时间:
2009-05
影响因子:
4.4
通讯作者:
Domínguez J
Domínguez J
中科院分区:
农林科学2区
文献类型:
--
作者:
Revilla C;Poderoso T;Martínez P;Alvarez B;López-Fuertes L;Alonso F;Ezquerra A;Domínguez J

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抗体介导的抗原靶向特异性抗原呈递细胞(APC)受体是增强T细胞对弱免疫原性抗原免疫应答的一种有吸引力的策略。在这里,我们描述了针对猪唾液黏附素(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到APC以刺激T细胞的潜力。这些单抗的特异性是通过对亲和纯化抗原衍生的肽的氨基酸序列分析确定的。猪锡蛋白是由巨噬细胞表达的,巨噬细胞存在于脾脏的白髓和红髓之间的边界以及淋巴结的包膜下窦,这是一个捕获血液和淋巴传播抗原的合适位置。它也通过肺泡巨噬细胞和单核细胞衍生的树突状细胞(MoDC)表达。血液单核细胞对该分子呈阴性,但IFN-a可诱导其表达。与Sn结合的MAb被迅速内吞。当使用小鼠免疫球蛋白免疫的猪T淋巴细胞作为应答细胞,IFN-a处理的单核细胞或MoDC作为APC时,针对唾液黏附素的单抗诱导体外T细胞增殖的浓度比非靶向对照单抗低100倍,这表明唾液黏附素在APC的抗原摄取和/或递送途径中起作用。
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-a. 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-a treated monocytes or MoDC as APC, suggesting a role of sialoadhesin in antigen uptake and/or delivery into the presentation pathway in APC.
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