VARIABLE GENE UTILIZATION IN SPECIFIC T CELL RESPONSES

我们已经描述了一个实验模型，其中变体肽被 引入胎儿胸腺器官培养，以确定它们是否具有 促进确定的T细胞分化的能力 的特异性此类肽家族的鉴定开启了 直接解决MHC- 选择胸腺中成熟T细胞的相关肽， 一种特殊的外源肽， 在外围。一个被广泛讨论的模型表明， T细胞受体与MHC自身肽相互作用的亲和力 复合体可能导致积极的选择，而不是消极的选择， 胸腺 与大卫马古利斯（免疫学实验室， NIAID，NIH），我们将利用最新的进展， 促进可溶性受体分离的T细胞受体cDNA 分子。然后，我们将确定相对亲和力和动力学的 纯化的TCR与可溶性H-2Kb的复合物的结合 未修饰的配体或与结构上相关的肽类似物， 用于阳性选择表达该TCR的成熟T细胞。

We have described an experimental model in which variant peptides are introduced in fetal thymic organ culture to determine whether they have the ability to promote differentiation of T cells of a defined specificity. Identification of a family of such peptides opens the possibility of directly addressing the relationship between MHC- associated peptides that select a mature T cell in the thymus and the particular foreign peptide that induces activation of this same T cell in the periphery. One widely discussed model suggests that reduced affinity of interaction between T cell receptor and an MHC:self-peptide complex could result in positive rather than negative selection in the thymus. In collaboration with David Margulies (Laboratory of Immunology, NIAID, NIH), we will exploit recent advances in the ability to engineer T cell receptor cDNA to facilitate isolation of soluble receptor molecules. We will then determine the relative affinity and kinetics of binding of purified TCR for complexes of soluble H-2Kb with either unmodified ligands or with the structurally related peptide analogs that were employed to positively select mature T cells that express this TCR.