Germline-encoded amino acid-binding motifs drive immunodominant public antibody responses
Abstract
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. Description Antibodies GRAB their targets Different individuals will reproducibly generate antibodies against the same epitopes after exposure to a pathogen. However, the mechanisms driving the production of these “public antibodies” continue to be poorly understood. Shrock et al. used a phage display platform called VirScan to glean additional insights into this process. They found that many human V gene segments contained germline-encoded amino acid–binding (GRAB) motifs that bind particular amino acids and are essential for antibody recognition. Moreover, a…
How strong is the evidence?
Evidence Hub reads this as a cohort study, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence.
Read the paper
Related studies
- Diagnosis and management of glutaric aciduria type I – revised recommendations
- EZH2 Codon 641 Mutations are Common in BCL2-Rearranged Germinal Center B Cell Lymphomas
- Consensus guidelines for the diagnosis and management of pyridoxine‐dependent epilepsy due to α‐aminoadipic semialdehyde dehydrogenase deficiency
- Systemic Metabolomic Changes in Blood Samples of Lung Cancer Patients Identified by Gas Chromatography Time-of-Flight Mass Spectrometry
- Human OTULIN haploinsufficiency impairs cell-intrinsic immunity to staphylococcal α-toxin
- Discovery of Novel Recurrent Mutations in Childhood Early T-Cell Precursor Acute Lymphoblastic Leukemia by Whole Genome Sequencing - a Report From the St Jude Children's Research Hospital - Washington University Pediatric Cancer Genome Project
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.