I-EP BOUND SELF-PEPTIDES: IDENTIFICATION AND CHARACTERIZATION

I-EP 结合自肽：鉴定和表征

• 批准号: 7721478
• 负责人: PAUL M ALLEN
• 金额: $ 0.05万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-02-01 至 2009-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7721478
• 关键词: Allogenic; Binding; Bioinformatics; Class; Complex; Computer Retrieval of Information on Scientific Projects Database; Funding; G-Protein-Coupled Receptors; Graft Rejection; Grant; Institution; Molecular; Mus; Peptide/MHC Complex; Peptides; Process; Research; Research Personnel; Resources; Source; Specificity; T-Lymphocyte; United States National Institutes of Health; base; mouse genome; peptide G; peptide I

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.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 T细胞识别肽/同种异体MHC复合物是移植的主要原因 拒绝。所介绍的自肽和MHC分子都涉及。但是，同种异体反应性和自肽的贡献的分子基础仍然很差。鼠2.102 T细胞对Hb（64-76）/i-EK特异性，并且与I-EP具有异同。由2.102识别的天然自肽/I-EP复合物仍然未知。在这项研究中，我们表征了由I-EP自然处理和提出的肽，并使用此信息来定义鼠I-EP II类分子的结合基序。有趣的是，wefound认为，I-EP首选的P9锚固残留与由 其他I-E分子，尽管P1锚固残基是保守的。由于缺乏19个不同的鉴定自肽，缺乏2.102 T细胞的刺激，显示出对同种异答响应的特异性程度。结合基序用于搜索小鼠基因组中的候选2.102反应性异肽，该肽包含强P1和P9锚固残基，并具有先前识别的允许的TCR接触残基。鉴定出两个潜在的同种肽，但其中只有一种肽G蛋白偶联受体128能够刺激2.102 T细胞。 G 因此，蛋白质偶联受体128肽代表了一种候选同种肽，由2.102 T细胞与I-EP结合的2.102 T细胞专门识别，并使用生物信息学鉴定。这些研究强调了自肽在同种异体反应性中的特定参与。