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Antibody-Functionalized Peptidic Membranes for Neutralization of Allogeneic Skin Antigen-Presenting Cells

机译:抗体功能化的肽膜用于中和同种异体皮肤抗原的细胞。

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摘要

We report herein application of an in situ material strategy to attenuate allograft T cell responses in a skin transplant mouse model. Functionalized peptidic membranes were used to impede trafficking of donor antigen-presenting cells (dAPCs) from skin allografts in recipient mice. Membranes formed by self-assembling peptides (SAPs) presenting antibodies were found to remain underneath grafted skins for up to 6 days. At the host-graft interface, dAPCs were targeted by using a monoclonal antibody that binds to a class II MHC molecule (IAd) expressed exclusively by donor cells. Using a novel cell labeling near-infrared nanoemulsion, we found more dAPCs remained in allografts treated with membranes loaded with aI-Ad than without. In vitro, dAPCs released from skin explants were found adsorbed preferentially on aI-Ad membranes. Recipient T cells from these mice produced lower concentrations of interferon-gamma cultured ex vivo with donor cells. Taken together, the data indicate that the strategy has the potential to alter the natural course of rejection immune mechanisms in stringent allogeneic models.
机译:我们在这里报道了原位材料策略在皮肤移植小鼠模型中减弱同种异体移植T细胞应答的应用。功能化的肽膜被用来阻止来自受体小鼠皮肤同种异体移植的供体抗原呈递细胞(dAPC)的运输。发现由呈递抗体的自组装肽(SAPs)形成的膜保留在移植皮肤下长达6天。在宿主-移植物界面,使用与供体细胞专门表达的II类MHC分子(IAd)结合的单克隆抗体靶向dAPC。使用一种新型的细胞标记近红外纳米乳剂,我们发现,用aI-Ad膜处理的同种异体移植物中保留的dAPC比未使用的多。在体外,发现从皮肤外植体释放的dAPCs优先吸附在aI-Ad膜上。来自这些小鼠的受体T细胞产生较低浓度的与供体细胞离体培养的干扰素-γ。综上所述,数据表明该策略具有改变严格同种异体模型中排斥免疫机制的自然过程的潜力。

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