The kinetic stability of MHC class II: Peptide complexes is a key parameter that dictates immunodominance
The kinetic stability of MHC class II: Peptide complexes is a key parameter that dictates immunodominance
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DOI：
10.1016/j.immuni.2005.05.009
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发表时间：
2005-07-01
期刊：
影响因子：
32.4
通讯作者：
Sant, AJ
中科院分区：
文献类型：
--
作者：
Lazarski, CA;Chaves, FA;Sant, AJ
T细胞对外源抗原的启动反应了树突状细胞中受调节的抗原加工，随后归巢到淋巴结，T细胞和携带抗原的树突状细胞之间持续的相互作用，以及最终的选择性T细胞活化和分化。在这项研究中，我们验证了II类肽复合物的内在特性是决定新出现的CD4 T细胞反应特异性的关键决定因素的假设。我们发现免疫优势肽与II类分子的半衰期非常长（t(1/2) bb0 150小时），而隐肽的半衰期不到10小时。此外，最重要的是，通过使用肽穿梭载体和四种独立抗原，我们证明了肽表位的半衰期与其体内免疫原性之间存在直接的因果关系。总的来说，我们的结果表明，II类肽复合物的半衰期是决定诱导T细胞反应最终层次的主要参数。
T cell priming to exogenous antigens reflects regulated antigen processing in dendritic cells, subsequent homing to lymph nodes, sustained interactions between T cells and antigen-bearing dendritic cells, and, ultimately, selective T cell activation and differentiation. In this study, we test the hypothesis that an intrinsic property of the class II:peptide complex is a key determinant that dictates the specificity of an emerging CD4 T cell response. We found that immunodominant peptides possess extremely long half-lives with class II molecules (t(1/2) > 150 hr), whereas cryptic peptides displayed half-lives of less than 10 hr. Furthermore, and most importantly, by using a peptide shuttle vector and four independent antigens, we demonstrate a direct, causative relationship between the half-life of peptide epitopes and their immunogenicity in vivo. Taken collectively, our results suggest the half-life of class II:peptide complexes is the primary parameter that dictates the ultimate hierarchy of the elicited T cell response.