POLYMORPHIC NEURONAL SURFACE PROTEINS

许多在神经系统外起识别作用的蛋白质 属于同一个结构相关分子家族，HIBIT (HLA，Ia，b2-微球蛋白，免疫球蛋白，Thy-1）超家族。 遗传 研究表明，该家族的其他基因产物仍有待进一步研究。 鉴定 虽然该家族主要在淋巴系统中进行研究， 组织，它不限于淋巴组织：Thy-1是一个主要的细胞 神经元表面蛋白。 我们假设：（1）一些“新”的HIBIT 蛋白质在神经系统中，（2）像其他成员一样， 家庭，他们提供识别功能。 我们将利用技术， 在神经组织中发现了新的HIBIT蛋白。 我们 将使用已知HIBIT蛋白的单克隆抗体（MoAbs）来寻找 新的变种。 我们还将提高单克隆抗体的交叉反应性， 决定簇，以用作新的HIBIT蛋白的更一般的探针。 在 一般而言，我们的工作将显示如何MoAbs可用作探针， 多基因家族，特别是当常规分离和 分子的生物化学表征是困难的。 这将 适用于少量存在的蛋白质，或不能被 分离，因此必须在显微镜测定中进行比较。 我们 以前的工作说明了这项工作的临床相关性：我们有 在人类神经元细胞上发现了弱的HLA-A、B、C表达， 对神经元肿瘤的生长潜力有影响， 神经移植 在以后的研究中，我们将确定 可能的多态性（细胞与细胞、组织与组织等）新HIBIT 蛋白质;这将表明识别功能的类型，每个可能 发球。

Many proteins that serve recognition functions outside the nervous system belong to the same family of structurally-related molecules, the HIBIT (HLA, Ia, b2-microglobulin, immunoglobulin, Thy-1) superfamily. Genetic studies show that still othe gene products of this family remain to be identified. Although this family has primarily been studied in lymphoid tissue, it is not limited to lymphoid tissue: Thy-1 is a major cell surface protein of neurons. We hypothesize that: (1) Some "new" HIBIT proteins are in the nervous system, and (2) like the other members of this family, they serve recognition functions. We will exploit techniques I have used previously, to reveal new HIBIT proteins in neural tissue. We will use monoclonal antibodies (MoAbs) to known HIBIT proteins to look for new variants. We will also raise MoAbs to cross-reactive intra-family determinants, to be used as more general probes for new HIBIT proteins. In general terms, our work will show how MoAbs may be used as probes for multi-gene families, particularly when conventional isolation and biochemical characterization of the molecules are difficult. This would apply to proteins present in small quantities, or cell types that cannot be separated, and must therefore be compared in microscopic assays. Our previous work illustrates the clinical relevance of this work: We have found weak HLA-A,B,C expression on human cells of neuronal origin, which has implications concerning the growth potential of neuronal tumors, and neural transplants. In later studies, we will determine the nature of possible polymorphisms (cell to cell, tissue to tissue, etc.) of new HIBIT proteins; this will suggest the type of recognition function each might serve.