TRANSPLANTION ANTIGENS--EXPRESSION AND FUNCTION

描述(改编自调查者摘要)：无处不在的 表达的高度多态的经典1类MHC抗原参与 消除病毒感染、恶性转化和同种异体 细胞。相比之下，目前对寡晶性的了解很少。 非经典移植抗原。这些与β-2M相关的分子 在结构上与经典的1类蛋白相似，但在模式上不同 以及表达水平和它们所关联的配体的类型。 我们研究的组织限制类分子是小鼠Qa-2 C57BL/10小鼠Q9基因编码的抗原。QA-2可以绑定不同的 与la类配体相似的多肽阵列，与 假设它可能参与抗原递呈给T细胞和/或 NK细胞对自然免疫的调节作用。黄曲霉毒素QA-2的鉴定 免疫优势组织及其限制性组织分布 提示这种分子可能具有新的或改变的功能 第一类抗原。这一假设将在拟议的 学习。具体目标是：1)构建转基因小鼠，表达 单链Qa-2(SCQ-2)是其唯一的生物化学丰富的1类 β2m基因缺陷C57BL/6小鼠的分子；2)详细表征 野生型Qa-2转录本的组织、细胞和肿瘤破坏 并将其与SCQa-2分子在组织中的分布进行比较 转基因小鼠；3)检测α/βT细胞和T细胞的发育 转基因小鼠中Qa-2抗原控制的反应；4)检测 Qa-2作为抑制性识别或积极识别的假说 NK受体的靶标。本文件中描述的研究结果 应用将允许评估模型组织的生物功能 特异性移植抗原Qa-2。这些信息可能会对 针对病原体和细菌的非限制性多肽疫苗的研究进展 肿瘤和在未来设计更有效的移植策略 和抑制自身免疫反应。

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.