FUNCTIONAL T CELL RECEPTOR GAMMA DELTA CELLS & GENES

存在两种T细胞受体(TCR)。TCR Alphabeta作为一种 二硫键连接的杂二聚体。TCRα和TCRα编码基因 β链与免疫球蛋白轻链和 由变量(V)、多样性(D)、连接(J)和 在T细胞中经历重排的恒定(C)区 个体发育学。已知TCRα-β淋巴细胞抗原识别 受到主要组织相容性(MHC)抗原的限制，但 受体基因片段使用， MHC限制和/或抗原识别仍不清楚。一个 外周血淋巴细胞上的第二T细胞受体异源二聚体 称为TCR伽马三角洲已被发现。TCR伽马三角洲 似乎起到了受体的作用，能够介导 伽马三角洲T细胞。然而，目前尚不清楚TCR伽马增量 在限制元件的背景下识别外来抗原， 类似的MHC I类和II类抗原。同样，这种关系 TCRγ-Delta基因片段使用与抗原识别之间的关系 尚未定义。因此，申请人建议 产生功能性抗原特异性和刺激细胞表面 蛋白质特异性TCRγ-Delta淋巴细胞系和克隆 重复刺激TCR伽马三角洲外周血 半致敏自体外周血单核细胞 细胞、同种异体细胞和肿瘤细胞系。TCR 然后将分析伽马三角洲淋巴细胞系和克隆 从功能上确定它们是否对 抗原(半抗原)和/或刺激细胞表面蛋白。这个 TCR Gamma和Delta基因使用的V、D和J基因片段 在这些品系和克隆上表达的内容将被评估以确定 基因片段使用与抗原特异性和免疫球蛋白的关系 涉及识别TCR-Gamma Delta靶细胞表面蛋白。 最后，对免疫异常患者进行筛查 将启动，以识别有异常的患者 在TCR中，γβ淋巴细胞功能或受体结构。这个 来自这类患者的TCR伽马三角洲受体将被表征 在蛋白质和基因水平上。

Two T cell receptors (TCR) exist. The TCR alphabeta exists as a disulfide-linked heterodimer. The genes encoding the TCR alpha and beta chains display homology with immunoglobulin light chains and are composed of variable (V), diversity (D), joining (J) and constant (C) regions which undergo rearrangements during T cell ontogeny. TCR alpha beta lymphocyte antigen recognition is known to be restricted by major histocompatibility (MHC) antigens, but the nature of the interaction between receptor gene segment usage, MHC restriction, and/or antigen recognition remains unclear. A second T cell receptor heterodimer on peripheral blood lymphocytes called TCR gamma delta has been identified. The TCR gamma delta appears to act as a receptor capable of mediating triggering of gamma delta T cells. However, it is unknown if the TCR gamma delta recognizes foreign antigens in the context of restriction elements, analogous MHC class I and II antigens. Similarly, the relationship between TCR gamma delta gene segment usage and antigen recognition has not been defined. Therefore, the applicant proposes to generate functional antigen-specific and stimulator cell surface protein-specific TCR gamma delta+ lymphocytes lines and clones by repetitively stimulating TCR gamma delta peripheral blood lymphocytes with haptenated autologous peripheral blood mononuclear cells, with allogeneic cells, and with tumor cell lines. The TCR gamma delta+ lymphocyte lines and clones will then be analyzed functionally to determine if they respond specifically to antigen(hapten) and/or to stimulator cell surface proteins. The V, D, and J gene segments used by the TCR gamma and delta genes expressed on these lines and clones will be evaluated to determine the relationship of gene segment usage to antigen specificity and to recognition of TCR gamma delta target cell surface proteins. Finally, a screening of patients with immunologic abnormalities will be initiated, in order to identify patients with abnormalities in TCR gamma delta+ lymphocyte function or receptor structure. The TCR gamma delta receptors from such patients will be characterized at the protein and gene level.