Modulation of CD4 T cell function by soluble MHC II-peptide chimeras.
Modulation of CD4 T cell function by soluble MHC II-peptide chimeras.
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DOI：
10.3109/08830180109045578
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发表时间：
2001-10-01
影响因子：
5
通讯作者：
Brumeanu, T D
中科院分区：
文献类型：
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作者：
Casares, S;Bona, C A;Brumeanu, T D
由抗原呈递细胞（APC）加工外源蛋白而衍生的长度为8至24个氨基酸残基的肽抗原，然后在由APC表达的主要组织相容性复合物分子（MHC）的背景下呈递给T细胞，是T细胞受体（TCR）的唯一生理配体。通过MHC II-肽复合物（信号1）共连接T细胞上的TCR和CD 4共受体导致各种T细胞功能，这取决于TCR和CD 4共连接的性质，以及共刺激受体（信号2）如CD 28、CTLA-4、CD 40 L是否参与这种相互作用。最近，基因工程的进展导致产生了一类新的TCR抗原特异性配体，即，可溶性MHC I类和MHC II类肽嵌合体。原则上，这些嵌合分子由抗原肽组成，所述抗原肽在MHC I分子的情况下共价连接至α链的氨基末端，或在MHC II分子的情况下共价连接至β链的氨基末端。从概念上讲，这种TCR/CD 4配体应向T细胞提供信号1。由于可溶性MHC-肽嵌合体在体外和体内对肽特异性T细胞表现出显著的调节作用，它们可能代表新一代免疫特异性T细胞调节剂，在自身免疫和感染性疾病中具有潜在的治疗应用性。这篇评论的重点是可溶性，MHC II类肽嵌合体的免疫调节作用，并讨论这些影响的背景下，最公认的理论对T细胞的调节。
Peptides antigens of 8 to 24 amino acid residues in length that are derived from processing of foreign proteins by antigen presenting cells (APC), and then presented to T cells in the context of major histocompatibility complex molecules (MHC) expressed by APC, are the only physiological ligands for T cell receptor (TCR). Co-ligation of TCR and CD4 co-receptor on T cells by MHC II-peptide complexes (signal 1) leads to various T cell functions depending on the nature of TCR and CD4 co-ligation, and whether costimulatory receptors (signal 2) such as CD28, CTLA-4, CD40L are involved in this interaction. Recently, the advance of genetic engineering led to the generation of a new class of antigen-specific ligands for TCR, i.e., soluble MHC class I-, and MHC class II-peptide chimeras. In principle, these chimeric molecules consist of an antigenic peptide which is covalently linked to the amino terminus of alpha-chain in the case of MHC I, or beta-chains in the case of MHC II molecules. Conceptually, such TCR/CD4 ligands shall provide the signal 1 to T cells. Since soluble MHC-peptide chimeras showed remarkable regulatory effects on peptide-specific T cells in vitro and in vivo, they may represent a new generation of immunospecific T cell modulators with potential therapeutic applicability in autoimmune and infectious diseases. This review is focused on the immunomodulatory effects of soluble, MHC class II-peptide chimeras, and discuss these effects in the context of the most accepted theories on T cell regulation.