Structural, thermodynamic and kinetic studies of antibo*

描述(由申请人提供) 免疫反应的亲和力成熟是免疫特有的过程。 系统。这一过程包括可变区的体细胞超突变 这导致免疫球蛋白亲和力显著增加 这些抗体是在体液免疫反应中激发的。对…的理解 这种现象的分子和结构基础是一个特殊的领域 对免疫学和一般生物科学的兴趣。 几位作者详细描述了亲和力成熟的模型 抗体-半抗原系统。然而，针对蛋白质抗原的亲和力成熟 没有被如此详细地描述过。我们以前的工作，就像在其他 实验室已经表明，在免疫反应过程中产生的抗体 对一种蛋白质抗原表现出快速成熟的亲和力，这是一种现象 与早期的Ig M-Ig G亚型类转换过程密切相关。不是 结构、序列或功能研究，描述发生在 在这一过程中可以发现抗蛋白质抗体的结合部位。 在当前的文学作品中。 这个项目的目的是表征序列和结合位点 结构井免疫球蛋白M未突变前体的结构 表征了抗鸡蛋清溶菌酶(HEL)的免疫球蛋白抗体。这一目标将 通过克隆和测序抗HEL IgM和X射线来完成 这些免疫球蛋白Fv片段的晶体结构测定。 重组Fv片段的结构、功能和突变研究 其中，免疫球蛋白M将揭示亲和力过程中产生的变化的本质 成熟。

DESCRIPTION (provided by applicant) Affinity maturation of the immune response is a process unique to the immune system. This process consists of somatic hypermutation of the variable domains of immunoglobulins, which leads to a significant increase in the affinities of the antibodies elicited during a humoral immune response. The understanding of the molecular and structural basis of this phenomenon is an area of particular interest for Immunology as well as the biological sciences in general. Several authors have described, in detail, models of affinity maturation in antibody-hapten systems. However, affinity maturation against protein antigens has not been described in such detail. Our previous work, as in other laboratories, has shown that the antibodies elicited during the immune response against a protein antigen show a fast maturation of the affinity, a phenomenon closely related to the early IgM-IgG isotype class switch process. No structural, sequence or functional studies describing the changes that occur at the combining site of anti-protein antibodies during this process can be found in the current literature. The aim of this project is to characterize the sequence and the binding site structures of the IgM unmutated precursors of the structurally well characterized IgG anti-hen egg-white lysozyme (HEL) antibodies. This goal will be accomplished by cloning and sequencing anti-HEL IgMs and by X-ray crystallographic structure determinations of the Fv fragments of these IgMs. Structural, functional and mutational studies of the recombinant Fv fragments of those IgMs would reveal the nature of the changes produced during affinity maturation.