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HIV superinfection elicits bnAbs more frequently than single infection, providing clues of how to elicit such responses. We used longitudinal antibody sequencing and structural studies to characterize bnAb development from a superinfection case. BnAb QA013.2 bound initial and superinfecting viral Env, despite its probable naive progenitor only recognizing the superinfecting strain, suggesting both viruses influenced this lineage. A 4.15 \u00c5 cryo-EM structure of QA013.2 bound to native-like trimer showed recognition of V3 signatures (N301\/N332 and GDIR). QA013.2 relies less on CDRH3 and more on framework and CDRH1 for affinity and breadth compared to other V3\/glycan-specific bnAbs. Antigenic profiling revealed that viral escape was achieved by changes in the structurally-defined epitope and by mutations in V1. These results highlight shared and novel properties of QA013.2 relative to other V3\/glycan-specific bnAbs in the setting of sequential, diverse antigens.<\/jats:p>","DOI":"10.7554\/elife.68110","type":"journal-article","created":{"date-parts":[[2021,7,15]],"date-time":"2021-07-15T08:00:44Z","timestamp":1626336044000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.68110","source":"Crossref","is-referenced-by-count":7,"title":["Functional development of a V3\/glycan-specific broadly neutralizing antibody isolated from a case of HIV superinfection"],"prefix":"10.7554","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7436-5622","authenticated-orcid":true,"given":"Mackenzie M","family":"Shipley","sequence":"first","affiliation":[{"name":"Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vidya","family":"Mangala 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