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.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 T 细胞对肽/同种异体 MHC 复合物的识别是移植的主要原因 拒绝。所呈现的自身肽和MHC分子都参与其中；然而，同种异体反应性的分子基础和自肽的贡献仍然不清楚。鼠 2.102 T 细胞对 Hb(64-76)/I-Ek 具有特异性，并且与 I-Ep 有同种反应性。 2.102 识别的天然自肽/I-Ep 复合物仍然未知。在本研究中，我们对 I-Ep 自然加工和呈递的肽进行了表征，并使用该信息来定义鼠 I-Ep II 类分子的结合基序。有趣的是，我们发现 I-Ep 偏好的 P9 锚残基与 I-Ep 偏好的残基完全不同。 其他 I-E 分子，尽管 P1 锚定残基是保守的。 19 种不同的已鉴定自肽对 2.102 T 细胞缺乏刺激，显示了同种异体反应的一定程度的特异性。结合基序用于在小鼠基因组中搜索候选 2.102 反应性同种肽，这些肽含有强 P1 和 P9 锚定残基，并具有先前鉴定的允许的 TCR 接触残基。鉴定出了两种潜在的同种肽，但这些肽中只有一种，即 G 蛋白偶联受体 128，能够刺激 2.102 个 T 细胞。 G 因此，蛋白偶联受体 128 肽代表了一种候选同种异体肽，它被与 I-Ep 结合的 2.102 T 细胞特异性识别，并使用生物信息学进行了鉴定。这些研究强调了自肽在同种异体反应中的具体参与。