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Germline-encoded amino acid-binding motifs drive immunodominant public antibody responses
Ist Teil von
Science (American Association for the Advancement of Science), 2023-04, Vol.380 (6640), p.eadc9498-eadc9498
Ort / Verlag
United States: The American Association for the Advancement of Science
Erscheinungsjahr
2023
Quelle
Science Online_科学在线
Beschreibungen/Notizen
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.