SPECIFIC RECOGNITION BY CLASS II ALLOREACTIVE T CELLS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 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。采用大规模筛选方法，包括60个新的I-Ek同种异体反应性T细胞和83个自然加工的自体肽，我们鉴定出9个T细胞具有匹配的刺激性自体多肽。这些T细胞中有6个识别单肽，具有与常规识别相同的特异性。其中三个T细胞被两到三个不同的多肽刺激，这些多肽没有序列同源性。这些多重反应性T细胞特异性地识别每个pMHC，但利用不同的I-Ek接触残基星座。这些研究表明，同种异体识别具有高度的特异性，每个T细胞都有固有的识别多个不同配体的能力，这为同种异体反应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. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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.