DEVELOPMENT OF ANTIBODY REPERTOIRES TO POLYSACCHARIDES

多糖抗体库的开发

• 批准号: 2073742
• 负责人: Richard A. Insel
• 金额: $ 16.88万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-09-30 至 1997-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2073742
• 关键词: Haemophilus influenzae vaccines; age difference; antibacterial antibody; antigen antibody reaction; bacterial polysaccharides; human subject; immunoconjugates; immunoglobulin genes; infant human (0-1 year); recombinant DNA

Protective immunity to infection from encapsulated bacteria is mediated predominantly by antibody (Ab) to their capsular polysaccharide (CP). The human Ab repertoire to the CP of such encapsulated bacteria is often highly restricted in diversity with use of a limited number of immunoglobulin heavy chain variable region (V/H) and light chain variable region (V/L) genes. The ontogeny of the human Ab response to the Haemophilus influenzae type b (Hib) Hib and multiple pneumococcal CP are delayed in the infant, which is the age of highest risk of infection with encapsulated bacteria. The mechanism of this delay in ontogeny is unknown. We hypothesize that contributing to this delay are poor expression of particular V genes and of N region addition, a process of nontemplated nucleotide addition mediated by the enzyme terminal deoxynucleotidyl transferase. N region addition is delayed in ontogeny in the mouse and particularly in murine CD5 positive B cells, which have been implicated in murine Ab production to CP. The aims of this proposal are to: 1) determine whether the neonate's kappa light chain variable region (Vkappa) repertoire is skewed compared to the adult's; 2) determine the ontogeny of N region addition at the Vkappa-Jkappa junction; 3) develop approaches to defining human Ab repertoires to CP. The results should provide insights into ontogeny of human Ab responses and a background for developing vaccines to prevent bacterial infections in infants.

介导对包囊细菌感染的保护性免疫 主要通过其荚膜多糖（CP）的抗体（Ab）。的 对这种被包囊的细菌的CP的人Ab库通常 在多样性方面受到高度限制， 免疫球蛋白重链可变区（V/H）和轻链可变区 区域（V/L）基因。人Ab对抗人IgG抗体的个体发生 流感嗜血杆菌B型（HiB）HiB和多重肺炎球菌CP是 延迟在婴儿，这是感染的最高风险的年龄， 包囊细菌 个体发育延迟的机制是 未知我们假设造成这种延迟的原因是穷人 特定V基因的表达和N区的添加， 酶末端介导的非模板核苷酸加成 脱氧核苷酸转移酶N区的加入在个体发育中是延迟的 在小鼠中，特别是在鼠CD 5阳性B细胞中， 涉及鼠抗CP抗体的产生。本提案的目的是 1）确定新生儿的κ轻链可变区是否 与成年人相比，Vkappa区域的所有功能都是偏斜的; 2） 确定在Vkappa-Jkappa的N区域添加的个体发育 连接; 3）开发定义CP的人类Ab谱系的方法。 这些结果将为人类抗体反应的个体发生提供见解 以及开发预防细菌感染疫苗的背景 在婴儿身上。