TRANSPLANTION ANTIGENS--EXPRESSION AND FUNCTION

移植抗原——表达和功能

• 批准号: 2886425
• 负责人: IWONA T STROYNOWSKI
• 金额: $ 30.19万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-06-01 至 2003-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2886425
• 关键词: MHC class I antigen; RNase protection assay; T lymphocyte; antigen presentation; antigen presenting cell; flow cytometry; genetically modified animals; histocompatibility antigens; immunocytochemistry; laboratory mouse; natural killer cells; thymus; tissue /cell culture

DESCRIPTION (Adapted from the Investigator's abstract): The ubiquitously expressed highly polymorphic classical class 1 MHC antigens participate in elimination of virally infected, malignantly transformed and allogeneic cells. In contrast very little is currently known about oligomorphic nonclassical transplantation antigens. These beta-2m-associated molecules resemble structurally the classical class 1 proteins but differ in patterns and levels of expression and the type of ligands that they associate with. The tissue-restricted class molecule that we study is the murine Qa-2 antigen encoded by the Q9 gene of C57BL/10 mice. Qa-2 can bind a diverse array of peptides similar to class la ligands, consistent with the assumption that it may be involved in antigen presentation to T-cells and/or regulation of natural immunity by NK cells. Identification of Qa-2 in immunologically-privileged tissue and its restricted tissue distribution suggest that this molecule may have novel or altered functions compared to the class 1 antigens. This hypothesis will be tested in the proposed studies. The specific aims are: 1) to construct transgenic mice expressing single-chain Qa-2 (SCQ-2) as their only biochemically abundant class 1 molecule in beta2m-deficient C57BL/6 mice; 2) to characterize in detail tissue, cell and tumor destruction of wild type Qa-2 transcripts and proteins and to compare it to tissue distribution of SCQa-2 molecules in the transgenic mice; 3) to examine development of alpha/beta T-cells and T-cell responses controlled by Qa-2 antigens in transgenic mice; 4) to test a hypothesis that Qa-2 functions as an inhibitory or a positive recognition target for NK receptors. The results of the studies described in this application will permit to assess biological functions of the model tissue specific transplantation antigen Qa-2. This information may be helpful in the development of unrestricted peptide vaccines against pathogens and tumors and in future design of more efficient strategies for transplantation and suppression of autoimmune reactions.

描述（改编自研究者摘要）：无处不在的 表达的高度多态性经典1类MHC抗原参与 消除病毒感染、恶性转化和同种异体 细胞 与此相反，目前很少有人知道寡形 非经典移植抗原 这些β-2m相关分子 结构上类似于经典的1类蛋白质，但模式不同 以及表达水平和与之相关的配体类型。 我们研究的组织限制性类分子是鼠Qa-2 C57 BL/10小鼠Q9基因编码的抗原。 Qa-2可以结合多种 类似于Ia类配体的肽阵列，与 假设它可能参与抗原呈递给T细胞和/或 NK细胞对自然免疫的调节。 中Qa-2的鉴定 免疫豁免组织及其受限组织分布 这表明，这种分子可能具有新的或改变的功能相比， 1类抗原。 这一假设将在拟议的 问题研究 具体目的是：1）构建表达外源基因的转基因小鼠 单链Qa-2（SCQ-2）作为它们唯一的生物化学丰富的1类 分子在β 2 m缺陷型C57 BL/6小鼠中的表达; 2）详细表征 野生型Qa-2转录物的组织、细胞和肿瘤破坏， 蛋白质，并将其与SCQa-2分子的组织分布进行比较， 转基因小鼠; 3）检查α/β T细胞和T细胞的发育 在转基因小鼠中由Qa-2抗原控制的应答; 4）测试一种 Qa-2作为抑制性或正性识别功能的假说 针对NK受体。 本研究中描述的研究结果 应用将允许评估模型组织的生物学功能 特异性移植抗原Qa-2。 这些信息可能有助于 开发针对病原体的非限制性肽疫苗， 肿瘤和未来设计更有效的移植策略 和抑制自身免疫反应。