Germline-encoded amino acid-binding motifs drive immunodominant public antibody responses.
Germline-encoded amino acid-binding motifs drive immunodominant public antibody responses.
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DOI：
10.1126/science.adc9498
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发表时间：
2023-04-07
期刊：
影响因子：
--
通讯作者：
中科院分区：
文献类型：
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尽管抗体库多种多样，但受感染的个体通常会对抗原内完全相同的表位产生抗体反应。支持这种现象的免疫机制仍然未知。在这里，通过以高分辨率绘制 376 个免疫显性“公共表位”并表征其几种同源抗体，我们得出结论，抗体中的种系编码序列驱动重复识别。对抗体-抗原结构的系统分析发现重和轻 V 基因片段内有 18 个人类和 21 个部分重叠的小鼠种系编码的氨基酸结合 (GRAB) 基序，在案例研究中，这些基序对于公共表位识别至关重要。 GRAB 基序代表了免疫系统结构的基本组成部分，可确保抗体识别病原体并促进物种特异性的可重复反应，从而对病原体施加选择性压力。抗体基因含有 GRAB 基序，可结合特定氨基酸并驱动个体对某些免疫显性表位的可重复反应。
Despite the vast diversity of the antibody repertoire, infected individuals often mount antibody responses to precisely the same epitopes within antigens. The immunological mechanisms underpinning this phenomenon remain unknown. Here, by mapping 376 immunodominant “public epitopes” at high resolution and characterizing several of their cognate antibodies, we conclude that germline-encoded sequences in antibodies drive recurrent recognition. Systematic analysis of antibody–antigen structures uncovered 18 human and 21 partially overlapping mouse germline-encoded amino acid-binding (GRAB) motifs within heavy and light V gene segments which, in case studies, are critical for public epitope recognition. GRAB motifs represent a fundamental component of the immune system’s architecture that ensures antibody recognition of pathogens and promotes species-specific reproducible responses that can exert selective pressure on pathogens. Antibody genes harbor GRAB motifs that bind specific amino acids and drive reproducible responses to certain immunodominant epitopes across individuals.
影响因子：
3.6
作者：
Robert R;Lefranc MP;Ghochikyan A;Agadjanyan MG;Cribbs DH;Van Nostrand WE;Wark KL;Dolezal O
通讯作者：
Dolezal O
影响因子：
3.7
作者：
Gorny MK;Sampson J;Li H;Jiang X;Totrov M;Wang XH;Williams C;O'Neal T;Volsky B;Li L;Cardozo T;Nyambi P;Zolla-Pazner S;Kong XP
通讯作者：
Kong XP