Genetic and environmental factors associated with the diversity and biases of immune system
作者单位：BGI-Shenzhen China National GeneBankBGI-Shenzhen
会议名称：《第十三届全国免疫学学术大会》
会议日期：2018年
学科分类：1001[医学-基础医学(可授医学、理学学位)] 100102[医学-免疫学] 10[医学]
关 键 词：T-cell receptor immune system whole genome sequencing clinical examination HLA
摘 要：The extremely large diversity of T-cell receptor(TCR) repertoire make up of individual immune system, acting against the external Pathogenic infection and enabling individual to keep healthy. The process of germline VDJ rearrangement, that comprise of VDJ gene recombination and random nucleotides deleted or inserted during the junction of V-D and D-J regions, contribute the huge TCR diversity and is regulated by both genetic factors and environment stimulation. The genetic influence are involved during the period of negative and positive selection of T cells in thymus and external antigen presentation. Additionally, auto or exogenous antigen stimulation causes some TCRs expansion. To explore how genetic factors and environment stimulation regulate the diversity of TCR repertoire, we collected more than 1000 volunteers and all were amplified TCR β repertoire and sequenced using high throughput sequencer. Simultaneously, multi-dimensional data were generated, including whole genome sequences(WGS), clinical tests, metabolomes, microbiomes, tumor screen, psychological test and so on. Using all of these data, we utilized bioinformatic method to identify genetic variations from WGS data associated with TCR β V genes and overall clone diversity, and found many associated variations in major histocompatibility complex(MHC) region. According to comparison of TCR repertoire and internal/external environmental data, we can find which factors are strong correlated with the diversity of TCRs. Our results clearly demonstrate the genetic environmental factors regulate the diversity of TCR repertoires, which provide clues for avoiding decreasing the capacity of immune system, and prevention and therapy of immune related disease.