SPECIFIC RECOGNITION BY CLASS II ALLOREACTIVE T CELLS

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 同种异体反应性T细胞的分子基础及其对pMHC配体的特异性/简并性仍未解决。 使用涉及60种新的I-Ek同种异体反应性T细胞和83种天然加工的自身肽的大规模筛选方法，我们鉴定了9种T细胞，其中存在匹配的刺激性自身肽。 这些T细胞中的六个识别具有与常规识别观察到的相同特异性的单个肽。 其中三种T细胞被两种或三种不同的肽刺激，这些肽没有序列同源性。 这些多重反应性T细胞特异性识别每种pMHC，但利用不同的I-Ek接触残基星座。 这些研究揭示了同种异体识别是高度特异性的，并且每个T细胞具有识别多种不同配体的固有能力，这为同种异体反应性的高频率提供了解释。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The molecular basis for alloreactive T cells and their specificity/degeneracy for pMHC ligands remain unresolved. Using a large scale screening approach involving 60 novel I-Ek alloreactive T cells and 83 naturally processed self-peptides, we identified nine T cells for which there were matching stimulatory self-peptides. Six of these T cells recognized single peptides with the same specificity observed for conventional recognition. Three of the T cells were stimulated by two or three distinct peptides, which had no sequence homology. These multiply reactive T cells recognized each pMHC specifically, but utilized distinct constellations of I-Ek contact residues. These studies reveal that allorecognition is highly specific, and that each T cell has an inherent capacity to recognize multiple distinct ligands, providing an explanation for the high frequency of alloreactivity.