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

Autor: Shrock EL; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.; Division of Genetics, Department of Medicine, Howard Hughes Medical Institute, Brigham and Women's Hospital, Boston, MA 02115, USA.; Program in Biological and Biomedical Sciences, Harvard University, Boston, MA 02115, USA., Timms RT; Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, University of Cambridge, Cambridge, UK., Kula T; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.; Division of Genetics, Department of Medicine, Howard Hughes Medical Institute, Brigham and Women's Hospital, Boston, MA 02115, USA.; Program in Biological and Biomedical Sciences, Harvard University, Boston, MA 02115, USA., Mena EL; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.; Division of Genetics, Department of Medicine, Howard Hughes Medical Institute, Brigham and Women's Hospital, Boston, MA 02115, USA., West AP Jr; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA., Guo R; Division of Infectious Disease, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.; Department of Microbiology, Harvard Medical School, Boston, MA 02115, USA.; Broad Institute of Harvard and MIT, Cambridge, MA, 02142, USA., Lee IH; Center for Systems Biology, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA., Cohen AA; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA., McKay LGA; National Emerging Infectious Diseases Laboratories, Boston University School of Medicine, Boston University, Boston, MA 02118, USA., Bi C; Division of Allergy and Immunology, Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.; Massachusetts Consortium on Pathogen Readiness, Boston, MA 02115, USA., Leng Y; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.; Division of Genetics, Department of Medicine, Howard Hughes Medical Institute, Brigham and Women's Hospital, Boston, MA 02115, USA., Fujimura E; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.; Division of Genetics, Department of Medicine, Howard Hughes Medical Institute, Brigham and Women's Hospital, Boston, MA 02115, USA., Horns F; Department of Bioengineering, Department of Applied Physics, Chan Zuckerberg Biohub and Stanford University, Stanford, CA 94305, USA., Li M; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.; Division of Genetics, Department of Medicine, Howard Hughes Medical Institute, Brigham and Women's Hospital, Boston, MA 02115, USA., Wesemann DR; Broad Institute of Harvard and MIT, Cambridge, MA, 02142, USA.; Division of Allergy and Immunology, Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.; Massachusetts Consortium on Pathogen Readiness, Boston, MA 02115, USA.; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, 02139 USA., Griffiths A; National Emerging Infectious Diseases Laboratories, Boston University School of Medicine, Boston University, Boston, MA 02118, USA., Gewurz BE; Division of Infectious Disease, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.; Department of Microbiology, Harvard Medical School, Boston, MA 02115, USA.; Broad Institute of Harvard and MIT, Cambridge, MA, 02142, USA.; Graduate Program in Virology, Division of Medical Sciences, Harvard Medical School, Boston, MA 02115, USA., Bjorkman PJ; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA., Elledge SJ; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.; Division of Genetics, Department of Medicine, Howard Hughes Medical Institute, Brigham and Women's Hospital, Boston, MA 02115, USA.
Jazyk: angličtina
Zdroj: Science (New York, N.Y.) [Science] 2023 Apr 07; Vol. 380 (6640), pp. eadc9498. Date of Electronic Publication: 2023 Apr 07.
DOI: 10.1126/science.adc9498
Abstrakt: 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.
Databáze: MEDLINE
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