FUNCTIONAL ROLE OF BETA 2 MICROGLOBULIN

该项目的目标有两个重点。 一是项目 概述了扩展当前正在进行的研究的方法， 解决β-2巨球蛋白（B2 m）在I类结构中的作用， 功能 第二，该项目概述了确定 导致无效B2 m/I类表达的机制 建立乳腺癌细胞系MDA-MB-157。 先前的结果有 证明在人B2 m交换后，Ltk-转染子 表达H-2Ld的小鼠表现出34-1-2抗体交叉反应的显著增加。 反应性 随后的研究证实，人类B2 m诱导 34-1-2交叉反应性，通过赋予内的构象变化， I类α-1螺旋区。 本文介绍的方法将侧重于 在清楚地辨别B2 m特异性氨基酸位置上， 在α-1螺旋区域上施加结构影响， 在I类/肽相互作用中重要。 此外， I类分子在构象上是柔性的，因此易受 还将研究由B2 m引起的结构扰动。 其他 以前的结果也表明B2 m突变是导致 用于乳腺癌细胞系MDA-MB-157的I类无效表达。 鉴定B2 m内发生的新突变事件 从癌细胞中分离的基因，可以提供洞察; 1） B2 m和I类的结构/功能关系，和2）机制 参与B2 m和I类基因表达。 鉴于该项目将 重点阐明B2 m在I类功能、分支、 I类分子在免疫系统监视中的作用， 监管将如此处理。

The aims of the project are two-fold in focus. First, the project outlines approaches which extend current research in progress designed to address the role beta-2 macroglobulin (B2m) plays in class I structure and function. Secondly, the project outlines approaches to identify mechanism(s) leading to null B2m/class I expression seen for an established breast cancer cell line, MDA- MB-157. Previous result have demonstrated that following human B2m exchange, an Ltk- transfectant expressing H-2Ld exhibits a marked increase in 34-1-2 antibody cross- reactivity. Subsequent studies substantiated that human B2m induced 34-1-2 cross-reactivity by imparting a conformational change within the alpha-1 helical region of class I. Approaches presented herein will focus on clearly discerning B2m specific amino acid positions involved in imparting structural influence over the alpha-1 helica region, a region important in class I/peptide interaction. In addition, the level to which class I molecules are conformationally flexible and hence susceptible to structural perturbations induced by B2m will also be investigated. Other previous results have also demonstrated that B2m mutations are responsible for null class I expression for a breast cancer cell line, MDA-MB-157. Identification of novel mutational events that have occurred within B2m genes isolated from cancer cells, could provide insight into; 1) the structure/function relationship of B2m and class I, and 2) mechanisms involved in B2m and class I gene expression. Given that the project will focus on clarifying the role B2m plays in class I function, ramifications for the role class I molecules play in immune system surveillance and regulation will so be addressed.