EVOLUTION OF IMMUNE RECOGNITION AND EVASION

免疫识别和逃避的进化

• 批准号: 3303062
• 负责人: AUSTIN L. HUGHES
• 金额: $ 4.28万
• 依托单位: PENNSYLVANIA STATE UNIVERSITY, THE
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-09-01 至 1997-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3303062
• 关键词: Anura; T cell receptor; alleles; aminoacid; antibody receptor; binding proteins; biochemical evolution; gene expression; genetic polymorphism; genetic regulatory element; globulins; glycoproteins; histocompatibility gene; host organism interaction; major histocompatibility complex; mathematical model; membrane channels; natural selections; nucleic acid sequence; statistics /biometry

The vertebrate immune system includes numerous interacting proteins involved in the recognition and elimination of parasitic organisms. The general goal of this research is to understand the evolution of key molecular components of this system, particularly the molecules encoded by the major histocompatibility complex (MHC), and to understand how immunogenic proteins of parasitic organisms have evolved under natural selection exerted by the host's immune system. The MHC is a multi-gene family encoding cell-surface glycoproteins which play an important role in the immune system, binding foreign peptides and presenting them to T cells, thereby triggering an appropriate immune response. Certain MHC loci are highly polymorphic in humans and other vertebrates, and recent analyses of DNA sequence data have provided evidence that this polymorphism is maintained by positive selection favoring the ability to bind and present a variety of foreign peptides. Therefore the MHC provides an excellent system for studying the evolution of immune recognition and the role of infectious disease as an agent of natural selection. The methods will involve statistical analysis of published DNA sequences, of which there are a large number now available for MHC genes of several mammalian species; for other immune system genes; and for genes of parasites encoding immunogenic proteins. The purpose of these analyses will be as follows: (1) to test the hypothesis that polymorphism at MHC loci is maintained by overdominant selection relating to disease resistance and to understand the role of recombination in generating new MHC alleles; (2) to test the hypothesis that the vertebrate immune system has exerted selection on proteins of parasitic organisms to evade recognition by the host; and (3) to understand the evolutionary history and patterns of co-evolution of MHC genes and other genes playing important roles in the immune system (including T cell receptors, integrins, Fc receptors, the C3/C4/C5 complement component family, and the ABC family of transmembrane transporters).

脊椎动物免疫系统包括许多相互作用的蛋白 参与了寄生生物的识别和消除。 这 这项研究的一般目标是了解密钥的演变 该系统的分子成分，尤其是编码的分子 由主要的组织相容性复合物（MHC），并了解 寄生生物的免疫原性蛋白在天然下进化 宿主的免疫系统采取的选择。 MHC是多基因 编码细胞表面糖蛋白的家庭，起着重要作用 在免疫系统中，将外肽结合并将其呈现给T 细胞，从而触发适当的免疫反应。 某些MHC 基因座在人类和其他脊椎动物中是高度多态的，最近 DNA序列数据的分析提供了证据表明 通过积极的选择有利于能力的能力来维持多态性 结合并呈现各种外肽。 因此MHC 提供了研究免疫进化的绝佳系统 识别和传染病作为自然毒剂的作用 选择。 该方法将涉及已发布的统计分析 DNA序列，其中有大量的MHC可用 几种哺乳动物物种的基因；用于其他免疫系统基因；和 用于编码免疫原性蛋白的寄生虫基因。 目的 这些分析将如下：（1）检验以下假设。 MHC基因座的多态性通过相关的过度选择来维持 抗病性并了解重组的作用 生成新的MHC等位基因； （2）检验以下假设 脊椎动物免疫系统已在寄生的蛋白质上进行选择 有机体逃避宿主的认可； （3）了解 MHC基因和其他共同进化的进化史和模式 基因在免疫系统中起重要作用（包括T细胞 受体，整合素，FC受体，C3/C4/C5补体组件 家族和ABC跨膜转运蛋白家族）。