摘要
为阐明免疫球蛋白(Ig)和T细胞受体(TCR)在抗体多样性产生机理上的异同,作者比较了Ig重链可变段(Ig V_H)和TCR可变段(TCR V)的密码子替代率和协同进化,并分析异同的原因。共搜集8种鼠和3种人的TCR α链可变段(V_α),11种鼠和1种人的TCRβ链可变段(V_β),以及2种鼠和4种人的T细胞γ链可变段;同时搜集11种鼠、3种人、3种南美鳄鱼和1种鲨鱼的Ig V_(H_(o))研究结果揭示:(1)对编码蛋白质的密码子来说,TCR V(包括V_α和V_β)的核苷酸替代率为Ig V_H的2.4倍,说明前者有更高的替代率。(2)以协同进化而言,TCR V和Ig V_H的基因重复率分别为1.7×10^(-6)和1.6×10^(-6)/基因年。两者几乎相同,均系低速保持者。TCR V的数目(V_α为100,V_β为30)远少于Ig V_H(数目为300),原因是前者受到主要组织相容性复合体的制约,即受到负选择,这与中性学说观点相一致。文章还讨论了体细胞突变和DNA重排对两类抗体多样性产生上的作用,并探讨了IgV_H和TCR V的假基因问题。
In order to explain difference and similarity in producing antibody diversity between im-munogJobulin (Ig) and T cell receptor (TCR),authors compared both codon substitution and concerted evolution rate between the variable segment of Ig heavy (Ig VB) and that of TCR (TCR V).The protein sequences of TCR Va (including 8 gene segments from mouse and 3 from human),TCR V?(including 11 from mouse and one from human) and T cell Vr (including Z from mouse and 4 from human) were compiled,as well as the protein sequences of Ig VH (3 from human,11 from mouse,3 from caiman and one from shark) were collected.It is shown that:(1) the nucleotide substitution of TCR V segment is 2.4 times as large as that of Ig Vn in coding region; (2) as for concerted evolution,gene duplicate rates in TCR V and Ig VH are 1.7×10-2 and 1.6 X 10-2/gene/year,respectively.The number of TCR V(V?equals to 100 and V2 equals to 30) is less than the one of Ig VH (VB equals to 300),for TCR V is subjecr to negative selection of major histocompatibility complex according to the neutral theory.We discussed that is somatic mutation or DNA rearrangement the main force in producing antibodv diversity and are there pseudogenes in TCR V or not.
关键词
免疫球蛋白
T细胞受体
分子进化
Molecular evolution,Concerted evolution,Immunoglobulin,T cell receptor,Neutral theory
