Evolution of Immune Recognition and Evasion

免疫识别和逃避的进化

• 批准号: 6738059
• 负责人: AUSTIN L. HUGHES
• 金额: $ 15.81万
• 依托单位: UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA
• 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 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6738059
• 关键词: Anura; DNA virus; alleles; alternatives to animals in research; antibody receptor; biochemical evolution; gene duplication; gene expression; genetic polymorphism; genetic recombination; genetic regulatory element; glycoproteins; histocompatibility gene; host organism interaction; immunity; major histocompatibility complex; mathematical model; molecular shape; natural selections; nucleic acid sequence; protein binding; protein sequence; statistics /biometry

DESCRIPTION (provided by applicant): The vertebrate immune system includes numerous proteins involved in the recognition and elimination of parasitic organisms. The general goals of this research are to understand the origin and evolution of key molecular components of this system, especially the molecules encoded by the genes of the major histocompatibility complex (MHC), and to understand the evolution of molecular adaptations in parasitic organisms that evade recognition and elimination 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 proteins and presenting them to T cells. Several of the MHC loci are highly polymorphic, and there is evidence that this polymorphism is maintained by balancing selection relating to most host immune surveillance. The methods used in this research involve statistical analysis of published DNA sequence data, of which a large amount is now available both for immune system genes and for genes of major human pathogens (particularly viruses). The purposes of these analyses are as follows: (1) to understand the evolutionary origin of MHC class I peptide-binding specificities; (2) to understand the evolutionary origin of MHC-related molecules that have assumed other functions; (3) to test the hypothesis that selection exerted by the host class I MHC and cytotoxic T cell (CTL) recognition system has played a role in the long-term evolution of viruses infecting vertebrates (including human immunodeficiency virus 1, hepatitis B virus, and papilloma viruses); (4) to understand the evolution of overlapping reading frames in viral genomes, with particular emphasis on the role of natural selection exerted by the host class I MHC/CTL recognition system on genes encoded by overlapping reading frames; (5) to understand the process by which the genomes of large DNA viruses (including adenoviruses, herpes viruses, poxviruses and baculoviruses) have "captured" host genes over the course of their evolution, a process which has enabled these viruses to obtain genes encoding immuno-modulating proteins which can interfere with host immune processes; and (6) to understand the evolution of repeat-containing proteins, which are believed to enable parasites to evade the highly specific recognition mechanisms of the host MHC and T cell system, in the genomes of the malaria parasites and DNA viruses.

描述（由申请人提供）：脊椎动物免疫系统包括许多参与识别和消除寄生生物的蛋白质。这项研究的总体目标是了解该系统的关键分子成分的起源和演变，尤其是由主要组织相容性复合物（MHC）基因编码的分子，并了解寄生生物中分子适应性的演化，这些寄生生物会被宿主的免疫系统逃避和消除。 MHC是一个编码细胞表面糖蛋白的多基因家族，在免疫系统中起重要作用，结合异物蛋白并将其呈现为T细胞。几个MHC基因座是高度多态性的，有证据表明，通过平衡与大多数宿主免疫监测相关的选择来维持这种多态性。这项研究中使用的方法涉及对已发表的DNA序列数据的统计分析，现在可以大量用于免疫系统基因和主要人类病原体（尤其是病毒）的基因。这些分析的目的如下：（1）了解MHC I类肽结合特异性的进化起源； （2）了解具有其他功能的MHC相关分子的进化起源； （3）检验以下假设：宿主I类MHC和细胞毒性T细胞（CTL）识别系统的选择在感染脊椎动物的病毒的长期演化中发挥了作用（包括人免疫缺陷病毒1，肝炎B病毒和乳头状瘤病毒）； （4）了解病毒基因组中重叠的阅读框的演变，特别是托管I类MHC/CTL识别系统在通过重叠读取框上编码的基因上扮演的自然选择的作用； （5）了解大型DNA病毒的基因组（包括腺病毒，疱疹病毒，痘病毒和杆菌病毒）在其进化过程中具有“捕获”的宿主基因，这一过程使这些病毒能够获得这些病毒的基因，从而获得了可以编码免疫调节蛋白的基因，这些蛋白可以与宿主的宿主相互作用宿主免疫过程； （6）了解含有重复的蛋白的演变，据信这可以使寄生虫在疟原虫和DNA病毒的基因组中逃避宿主MHC和T细胞系统的高度特异性识别机制。