Germline-encoded amino acid-binding motifs drive immunodominant public antibody responses

• 成果类型: Article
• 署名作者: Shrock, Ellen L.; Timms, Richard T.; Kula, Tomasz; Mena, Elijah L.; West Jr, Anthony P.; Guo, Rui; Lee, I-Hsiu; Cohen, Alexander A.; McKay, Lindsay G. A.; Bi, Caihong; Keerti; Leng, Yumei; Fujimura, Eric; Horns, Felix; Li, Mamie; Wesemann, Duane R.; Griffiths, Anthony; Gewurz, Benjamin E.; Bjorkman, Pamela J.; Elledge, Stephen J.
• 署名单位: Harvard University; Harvard Medical School; Howard Hughes Medical Institute; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard University; University of Cambridge; California Institute of Technology; Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard University; Harvard Medical School; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard Medical School; Boston University; Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Brigham & Women's Hospital; Chan Zuckerberg Initiative (CZI); Stanford University; Harvard University; Massachusetts Institute of Technology (MIT); Ragon Institute; Harvard University; Harvard Medical School; Harvard University
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-11520
• DOI: 10.1126/science.adc9498
• 发表日期: 2023-04-01
• 关键词: gene usage; protein; sequence; epitope; RECOGNITION; PROTECTION; mutations; EVOLUTION; SYSTEM; IMPACT

摘要

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. By mapping 376 immunodominant public epitopes at high resolution and characterizing several of their cognate antibodies, we concluded 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 that in case studies proved critical for public epitope recognition. GRAB motifs represent a fundamental component of the immune system's architecture that promotes recognition of pathogens and leads to species-specific public antibody responses that can exert selective pressure on pathogens.