FUNCTIONAL ROLE OF BETA 2 MICROGLOBULIN

该项目的目标有两个重点。第一，项目 概述了扩展当前正在进行的研究的方法，旨在 解决β-2巨球蛋白(B2M)在I类结构和 功能。其次，该项目概述了确定 导致空B2M/I类表达的机制(S) 建立了乳腺癌细胞系--MDA-MB-157。以前的结果是 证明了在人类B2M交换后，一种Ltk-转染体 表达H-2LD后，34-1-2抗体交叉率显著增加 反应性。随后的研究证实，人类B2M导致 34-1-2通过给予构象变化的交叉反应 阿尔法-1螺旋区的I类，这里提出的方法将重点 关于明确识别B2M参与的特定氨基酸位置的问题 对α-1螺旋区域的结构影响 在I类/肽相互作用中很重要。此外，达到的水平 I类分子在构象上是柔性的，因此容易受到 还将研究B2M引起的结构扰动。其他 以前的结果也证明了B2M突变是 乳腺癌细胞系MDA-MB-157的I类基因表达为零。 B2M中发生的新突变事件的鉴定 从癌细胞中分离的基因，可以提供对以下方面的洞察：1) B2M和I类的结构/功能关系，以及2)机构 参与B2M和I类基因的表达。鉴于该项目将 重点阐明B2M在I类功能、分支中扮演的角色 对于I类分子在免疫系统监测中扮演的角色 监管问题将会得到解决。

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.