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首页> 外文学位 >MOLECULAR AND GENE TRANSFER STUDIES OF ANTI-(TYROSINE, GLUTAMIC ACID)-ALANINE--LYSINE HYBRIDOMA ANTIBODIES FROM C57BL/10 MICE (GERMLINE, SOMATIC MUTATION, DNA).
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MOLECULAR AND GENE TRANSFER STUDIES OF ANTI-(TYROSINE, GLUTAMIC ACID)-ALANINE--LYSINE HYBRIDOMA ANTIBODIES FROM C57BL/10 MICE (GERMLINE, SOMATIC MUTATION, DNA).

机译：来自C57BL / 10小鼠的抗-（酪氨酸，谷氨酸酸）-丙氨酸-赖氨酸纤溶性抗体的分子和基因转移研究（种系，体细胞突变，DNA）。

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摘要

A major function of the humoral immune system of higher vertebrates is to synthesize antibodies or immunoglobulin (Ig) molecules. These antibodies are responsible for binding a great number of foreign substances and rendering them harmless to the host organism. Most mammalian species (and other vertebrates as well) have the genetic capacity to generate 10('6) to 10('8) kinds of Ig molecules, each of which has a unique antigen-binding potential.; The studies presented here represent a dissection and reassembly of the immune response to the synthetic polypeptide antigen (T,G)-A--L. The first part of this work deals with the molecular biology of the murine response to (T,G)-A--L. Hybridoma cell lines secreting anti-(T,G)-A--L antibody have been generated and cloned. The phenotype of this response is of limited heterogeneity. The light chain restriction enzyme pattern is similar if not identical in most cell lines tested. Heavy chain patterns are more complex. Cloning and sequencing three of these genes has partially resolved the question of how this complexity arises. These hybridomas have rearranged the same germline Vh gene (186-2) but are heterogeneous with respect to the diversity (D) gene and joining (J) gene. Somatic mutations have taken place throughout the V gene and I have shown strong evidence to support parallel mutations in the complementarity-determining regions (CDR) 1 and 2.; The second part of this work describes studies of DNA-mediated gene transfer experiments transfecting heavy chain genes into a lymphoid variant cell line which secretes only anti-(T,G)-A--L light chains. These studies show that chimeric antibodies (Vh gene product from one hybridoma cell spliced to the C gene from another cell and associated with light chains from yet another cell) can be synthesized and secreted from host cells using gene transfer techniques. By using these transfectomas it will be possible eventually to study the function of novel chain and structures created in vitro and replanted in vivo for expression. These molecules have great potential as immunoregulatory and therapeutic agents.
机译：高等脊椎动物的体液免疫系统的主要功能是合成抗体或免疫球蛋白（Ig）分子。这些抗体负责结合大量外来物质，并使它们对宿主生物无害。大多数哺乳动物物种（以及其他脊椎动物）都具有产生10（'6）至10（'8）种Ig分子的遗传能力，每种分子都有独特的抗原结合潜力。本文介绍的研究代表了对合成多肽抗原（T，G）-A--L的免疫反应的解剖和重组。这项工作的第一部分涉及鼠对（T，G）-A--L反应的分子生物学。分泌抗-（T，G）-A--L抗体的杂交瘤细胞系已经产生并克隆。该反应的表型具有有限的异质性。如果在大多数测试的细胞系中不同，则轻链限制酶模式相似。重链模式更为复杂。这些基因中的三个的克隆和测序已部分解决了这种复杂性如何产生的问题。这些杂交瘤已重新排列了相同的种系Vh基因（186-2），但就多样性（D）基因和连接（J）基因而言是异质的。整个V基因都发生了体细胞突变，而且我已经显示出有力的证据支持互补决定区（CDR）1和2中的平行突变。这项工作的第二部分描述了DNA介导的基因转移实验的研究，该实验将重链基因转染到仅分泌抗（T，G）-A-L轻链的淋巴样细胞系中。这些研究表明，可以使用基因转移技术从宿主细胞合成并分泌嵌合抗体（来自一个杂交瘤细胞的Vh基因产物与另一个细胞的C基因剪接，并与另一个细胞的轻链相关）。通过使用这些转染瘤，最终将有可能研究体外产生并体内植入以表达的新型链和结构的功能。这些分子作为免疫调节剂和治疗剂具有巨大的潜力。

著录项

  • 作者

    CARMACK, CONDIE EDWIN.;

  • 作者单位

    The University of Utah.;

  • 授予单位 The University of Utah.;
  • 学科 Biology Molecular.; Health Sciences Immunology.
  • 学位 Ph.D.
  • 年度 1986
  • 页码 147 p.
  • 总页数 147
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 分子遗传学;预防医学、卫生学;
  • 关键词

  • 入库时间 2022-08-17 11:51:02

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