Antigen processing in the secretory pathway

分泌途径中的抗原加工

• 批准号: 7728304
• 负责人: Nilabh Shastri
• 金额: $ 37.76万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-02-15 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7728304
• 关键词: Aminopeptidase; Antigens; Autoimmunity; Books; CD8B1 gene; Cell surface; Cells; Complex; Cytoplasm; Endoplasmic Reticulum; Goals; Immune; Immune response; Immune system; Ligands; MHC Class I Genes; Mass Spectrum Analysis; Mediating; Modeling; Mus; Pathway interactions; Peptide Hydrolases; Peptide/MHC Complex; Peptides; Principal Investigator; Process; Research; Structure; Surface; T-Lymphocyte; Text; Tissues; abstracting; antigen processing; immunogenic; immunogenicity; improved; neoplastic cell; novel; programs; response

Nilabh, 2 R01 Al 060040-06A1 NiJabh, ROl AI 060040-06A 1 ABSTRACT The long term goal of our research is to understand and manipulate research is to understand and manipulate immune surveillance. The antigen processing mechanisms yie,lds thousands of surveillance. The antigen processing yields thousands of peptide/MHC class II complexes (pMHC I) on the cell surface as potential ligands cell ligand COB Contrary to text book models for CD8 T cells. Contrary to text book models which often depict the final final antigenic peptide being generated in the cytoplasm, recent findings show that cytoplasm, findings that antigen processing continues in the endoplasmic reticulum (ER). The protease continues in the endoplasmic reticulum (ER). protease the trimming of antigenic that mediates the trimming of antigenic precursors in the ER is called ERAAP, fa ft associated with antigen processing. In ERAAP-deficien the ER aminopeptidase associated with antigen processing. In ERAAP-deficien mice. absence of ER trimming disrupts the normal self-pMHC IIrepertoire. Manv mice, trimming disrupts the normal self-pMHC repertoire. Mani pMHC I are missing and concomitantly a large set of novel pMHC I emerges on on the surface of ERAAP-deficient cells. The loss and gain of unique pMHC I cells. The loss and results in Vigorous reciprocal immune responses in wild-type versus ERAAP vigorous versus ERAAPdeficient mice. E Corn -cu Here we propose to fill the gaps in our understanding of (a) the structure we and origin of the unique immunogenic pMHC I generated in the absence of absence ERAAP, (b) global analysis of the pMHC I repertoire generated in the presence the presence or absence of ERAAP by mass-spectrometry, and (c) the cellular mechanisms mass-spectrometry, (c) the used for eliciting CD8 T cell responses to unique pMHC I in ERAAP deficient COB pMHC in ERAAP deficient antiger cells. We anticipate the results to provide a deeper understanding of the antiger We anticipate the results to provide a deeper understanding processing pathway and how the pathway can be manipulated to regulate can manipulated to regulate immunogenicity. moo '.. (0D Qom. cep cam coo -0'0

Nilabh，2 R01 Al 060040-06A1 NiJabh，角色AI 060040-06A 1 摘要 我们研究的长期目标是理解和操纵研究，理解和操纵免疫监视。对抗原的处理机制进行了数千次监测。抗原处理在细胞表面产生数千个肽/MHC II类复合体(PMHC I)，作为潜在的配体细胞配体COB，与教科书中CD8T细胞的模型相反。与通常描述最终抗原肽在细胞质中生成的教科书模型相反，最近的发现表明，在细胞质中，抗原处理在内质网(ER)中继续进行。蛋白水解酶在内质网(ER)中继续存在。蛋白水解酶：在内质网中调节抗原前体修剪的抗原修剪称为ERAAP，与抗原加工有关。在ERAAP缺乏的患者中，与抗原处理相关的ER氨基肽酶。在ERAAP缺陷小鼠中。缺乏内质网修剪会扰乱正常的自我pMHC II谱系。MANV小鼠，修剪扰乱了正常的自我pMHC谱系。MANI pMHC I缺失，伴随而来的是ERAAP缺陷细胞表面出现大量新的pMHC I。独特的pMHC I细胞的得失。在野生型与ERAAP强健与ERAAP缺陷小鼠中失去并导致强烈的互惠免疫反应。 E 玉米 -cu 在这里，我们建议填补我们在以下理解方面的空白：(A)在没有ERAAP的情况下产生的独特的免疫原性pMHC I的结构和来源，(B)通过质谱学对存在或不存在ERAAP的情况下产生的pMHC I谱系的全局分析，以及(C)质谱学的细胞机制，(C)用于在ERAAP缺陷的COB pMHC中诱导CD8 T细胞对独特的pMHC I的反应。我们期待的结果能提供对抗菌素更深层次的理解我们期待的结果能提供更深层次的理解处理途径，以及如何操纵该途径来调节CaN调节免疫原性。 Moo ‘.. (0d 库姆。 CEP 凸轮 首席运营官 -0‘0