I-EP BOUND SELF-PEPTIDES: IDENTIFICATION AND CHARACTERIZATION

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 中心，不一定是研究者的机构。 肽/同种异体MHC复合物的T细胞识别是移植的主要原因 排斥反应所提出的自身肽和MHC分子都参与其中;然而，同种异体反应性的分子基础和自身肽的贡献仍然不清楚。小鼠2.102 T细胞对Hb（64-76）/I-Ek具有特异性，并对I-Ep具有同种异体反应性。2.102识别的天然自身肽/I-Ep复合物仍然未知。在这项研究中，我们的特点是自然加工和提出的I-Ep的肽，并使用这些信息来定义的结合基序的小鼠I-Ep II类分子。有趣的是，我们发现I-Ep偏爱的P9锚残基与I-Ep偏爱的P9锚定残基完全不同。 其他I-E分子，尽管P1锚残基是保守的。同种异体反应的特异性程度显示缺乏刺激的2.102 T细胞由19种不同的识别selfpeptides。结合基序用于在小鼠基因组中搜索含有强P1和P9锚残基并具有先前鉴定的允许的TCR接触残基的候选2.102反应性同种异体肽。鉴定了两种潜在的同种异体肽，但这些肽中只有一种，G蛋白偶联受体128，能够刺激2.102 T细胞。国集团 因此，蛋白偶联受体128肽代表候选的同种异体肽，其被与I-Ep结合的2.102 T细胞特异性识别，并使用生物信息学鉴定。这些研究突出了自身肽在同种异体反应性中的具体参与。

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. T cell recognition of peptide/allogeneic MHC complexes is a major cause of transplant rejection. Both the presented self-peptides and the MHC molecules are involved; however, the molecular basis for alloreactivity and the contribution of self-peptides are still poorly defined. The murine 2.102 T cell is specific for Hb(64-76)/I-Ek and is alloreactive to I-Ep. The natural self-peptide/I-Ep complex recognized by 2.102 remains unknown. In this study, we characterized the peptides which are naturally processed and presented by I-Ep, and used this information to define the binding motif for the murine I-Ep class II molecule. Interestingly, wefound that the P9 anchor residue preferred by I-Ep is quite distinct from the residues preferred by other I-E molecules, although the P1 anchor residue is conserved. A degree of specificity for the alloresponse was shown by the lack of stimulation of 2.102 T cells by 19 different identified selfpeptides. The binding motif was used to search the mouse genome for candidate 2.102 reactive allo-peptides that contain strong P1 and P9 anchor residues and possess previously identified allowable TCR contact residues. Two potential allo-peptides were identified, but only one of these peptides, G protein-coupled receptor 128, was able to stimulate 2.102 T cells. The G protein-coupled receptor 128 peptide, thus, represents a candidate allo-peptide that is specifically recognized by 2.102 T cells bound to I-Ep and was identified using bioinformatics. These studies highlight the specific involvement of self-peptides in alloreactivity.