Fine specificity and sequence of antibodies directed against the ectodomain of matrix protein 2 of influenza A virus.
Fine specificity and sequence of antibodies directed against the ectodomain of matrix protein 2 of influenza A virus.
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DOI：
10.1016/j.molimm.2005.12.015
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发表时间：
2006-07
影响因子：
3.6
通讯作者：
Manxin Zhang;D. Zharikova;K. Mozdzanowska;L. Otvos;W. Gerhard
中科院分区：
文献类型：
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作者：
Manxin Zhang;D. Zharikova;K. Mozdzanowska;L. Otvos;W. Gerhard
基质蛋白2（M2 e）的胞外域在人甲型流感病毒中保持显著保守，并且是具有保护活性的Ab的靶标。出于这些原因，M2 e正在研究其作为广泛保护性甲型流感病毒疫苗的潜力。在这里，我们报告了从三只BALB/c小鼠分离的七种M2 e特异性mAb在不同免疫方案后的精细特异性和序列。mAb识别包含在对应于M2 e（4-16）的13 aa长肽内的表位。它们来源于4种不同的前体B细胞，并显示出高度限制性的可变（V）基因使用，因为它们的重链V区均由相同的VH、D和JH基因片段形成，而它们的轻链V区仅使用两种不同的Vκ基因（分别为Vκ19-15/IGKV 6 -15和Vκ8-30/IGKV 8 -30; NCBI/IMGT注释）。表达的VH基因的共有序列属于J558/HV 1家族。与BALB B/c种系基因J558.n/IGHV 1 S137的同源性为96%，与几种BALB B/c B-1 B细胞表达的VH基因的同源性为100%。这表明该共有序列是功能性BALB/c种系VH基因的共有序列。这种反应的遗传限制可能在一定程度上导致感染诱导的M2 e特异性Ab反应普遍较差。
The ectodomain of matrix protein 2 (M2e) has remained remarkably conserved amongst human influenza A viruses and is a target for Abs with protective activity. For these reasons, M2e is being investigated for its potential as a broadly protective influenza A virus vaccine. Here, we report on the fine specificity and sequence of seven M2e-specific mAbs isolated from three BALB/c mice after different immunization protocols. The mAbs recognized epitopes comprised within a 13aa long peptide corresponding to M2e(4-16). They originated from 4 distinct precursor B cells and showed a highly restricted variable (V) gene usage, in that their heavy chain V regions were all formed by the same VH, D and JHgene segments and their light chain V regions made use of only two distinct Vκ genes (Vκ19-15/IGKV6-15 and Vκ8-30/IGKV8-30; NCBI/IMGT annotation, respectively). The consensus sequence of the expressed VHgenes belongs to the J558/HV1 family. It showed 96% identity with the BALB/c germline gene J558.n/IGHV1S137 and 100% identity with a VHgene expressed by several BALB/c B-1 B cells. This suggests that the consensus sequence is that of a functional BALB/c germline VHgene. The genetic restriction of this response may in part underlie the generally poor M2e-specific Ab response induced by infection.