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

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.

Automated summary

Despite a diverse antibody repertoire, infected individuals often produce antibodies against the same epitopes within antigens. The underlying immunological mechanisms are still unknown. Mapping 376 immunodominant public epitopes and studying the corresponding antibodies, researchers found that germline-encoded sequences in antibodies play a role in recurrent recognition. They also identified human and mouse germline-encoded amino acid-binding (GRAB) motifs critical for public epitope recognition. Overall, GRAB motifs contribute to the immune system's architecture, promoting pathogen recognition and species-specific public antibody responses that can influence pathogens.