A divalent human leukocyte antigen-B7 fusion-protein up-regulates CD25 and CD69 in alloreactive CD8+ T cells bypassing CD28 costimulation
A divalent human leukocyte antigen-B7 fusion-protein up-regulates CD25 and CD69 in alloreactive CD8+ T cells bypassing CD28 costimulation
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DOI：
10.1097/01.tp.0000205770.07196.e6
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发表时间：
2006-05-15
期刊：
影响因子：
6.2
通讯作者：
Zavazava, Nicholas
中科院分区：
文献类型：
--
作者：
Rickert, Uta;Welke, Judith;Zavazava, Nicholas
背景。 T 细胞识别抗原呈递细胞上的主要组织相容性复合体 (MHC) 分子及其隐秘抗原肽，通常会被触发增殖，并且当足够时，可以进行共刺激。可溶形式的单体 MHC 分子可诱导细胞凋亡、无反应性或 T 细胞受体 (TCR) 的减少。方法。人类白细胞抗原 (HLA)-B7 的二聚体融合蛋白经过分子改造并在 B 细胞系中表达以允许分泌。根据标准方案生成同种反应性 T 细胞。结果。得到了类似160kD的二聚体；亲和纯化，用于研究 T 细胞相互作用。以固定化形式，该蛋白有效刺激同种异体反应性 T 细胞增殖并以浓度依赖性方式产生白细胞介素 (IL)-2 和干扰素 (IFN)-γ，从而上调 CD25 和 CD69 的表达。相反，可溶性融合蛋白诱导T细胞凋亡。结论。二价 MHC 融合蛋白对 T 细胞调节的二分性保证了在移植和自身免疫性疾病中使用 MHC 多聚体作为定制设计的免疫调节分子。
Background. T cells recognize major histocompatibility complex (MHC) molecules and their cryptic antigenic peptides on antigen-presenting cells and are generally triggered to proliferate, and when sufficient, co-stimulation is available. In soluble form, monomeric MHC molecules can induce apoptosis, anergy, or decreases of the T-cell receptor (TCR).Methods. A dimeric fusion protein of the human leukocyte antigens (HLA)-B7 was molecularly engineered and expressed in a B-cell line to allow secretion. Alloreactive T cells were generated according to the standard protocol.Results. A dimer of similar to 160 kD was obtained; affinity purified, and used to study T-cell interaction. In immobilized form, this protein efficiently stimulated alloreactive T cells to proliferate and produce interleukin (IL)-2 and interferon (IFN)-gamma in a concentration-dependent manner, up-regulating CD25 and CD69 expression. In contrast, the soluble fusion protein induced T-cell apoptosis.Conclusions. The dichotomy in T-cell regulation by a divalent MHC fusion protein warrants the use of MHC multimers as custom-designed immune-regulatory molecules both in transplantation and autoimmune disease.