FUNCTIONAL T CELL RECEPTOR GAMMA DELTA CELLS & GENES

存在两种T细胞受体（TCR）。 TCR字母表作为一种 二硫键连接的异二聚体。 编码TCR α的基因和 β链显示与免疫球蛋白轻链的同源性， 由变量（V）、多样性（D）、连接（J）和 在T细胞增殖过程中经历重排的恒定（C）区 个体发育 已知TCR α β淋巴细胞抗原识别 受主要组织相容性（MHC）抗原的限制，但 受体基因片段使用之间相互作用的性质， MHC限制和/或抗原识别仍不清楚。 一 外周血淋巴细胞第二T细胞受体异源二聚体 称为TCR γ δ的基因已经被确认。 TCR γ δ 似乎作为一种受体，能够介导触发 γ δ T细胞 然而，目前尚不清楚TCR γ δ是否 在限制性元件的情况下识别外来抗原， 类似的MHC I类和II类抗原。 同样，关系 TCR γ δ基因片段的使用和抗原识别之间 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 蛋白特异性TCR γ δ +淋巴细胞系和克隆， 反复刺激TCR γ δ外周血 淋巴细胞与半抗原化自体外周血单核细胞 细胞、同种异体细胞和肿瘤细胞系。 的TCR 然后分析γ δ +淋巴细胞系和克隆 以确定它们是否对 抗原（半抗原）和/或刺激细胞表面蛋白。 的 TCR γ和δ基因使用的V、D和J基因片段 将评估在这些品系和克隆上表达的蛋白， 基因片段使用与抗原特异性的关系， TCR γ δ靶细胞表面蛋白的识别。 最后，对免疫异常患者进行筛查， 将启动，以识别异常患者 TCR γ δ +淋巴细胞功能或受体结构。 的 将表征来自这些患者的TCR γ δ受体 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.