POLYMORPHIC NEURONAL SURFACE PROTEINS

许多在神经系统外具有识别功能的蛋白质 属于相同的结构相关分子家族，HIBIT (H1a，Ia，b2-微球蛋白，免疫球蛋白，Thy-1)超家族。遗传 研究表明，这个家族的其他基因产物仍然存在 已确认身份。尽管这个家族的研究主要集中在淋巴系统 组织，它不限于淋巴组织：THY-1是一个主要细胞 神经元表面蛋白。我们假设：(1)一些“新的”HIBIT 蛋白质存在于神经系统中，并且(2)像这个物种的其他成员一样 家庭，它们起到识别的作用。我们将利用技术I 在神经组织中发现了新的HIBIT蛋白质。我们 将使用针对已知HIBIT蛋白的单抗(MoAbbs)来寻找 新的变种。我们还将提高MoAbs的家庭内交叉反应性 决定簇，用作新的HIBIT蛋白的更通用的探针。在……里面 总而言之，我们的工作将展示如何将MoAbs用作 多基因家族，特别是当常规分离和 对这些分子进行生化表征是困难的。这将会 适用于少量存在的蛋白质，或不能 分离出来，因此必须在显微镜下进行比较。我们的 之前的工作说明了这项工作的临床相关性：我们有 在神经细胞来源的人类细胞上发现弱的HLA-A，B，C表达，这 与神经性肿瘤的生长潜力有关，以及 神经移植。在以后的研究中，我们将确定 可能的多态(细胞到细胞、组织到组织等)新HIBIT的 蛋白质；这将暗示每种可能的识别功能的类型 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.