Trama, AMoody, MAAlam, SMJaeger, FLockwood, BParks, RLloyd, KStolarchuk, CScearce, RFoulger, AMarshall, DWhitesides, JJeffries, TWiehe, KMorris, LLambson, BSoderberg, KHwang, KTomaras, GVandergrift, NJackson, KLRoskin, KBoyd, SKepler, TLiao, HHaynes, B2014-08-132014-08-13https://hdl.handle.net/10161/9021Monoclonal antibodies derived from blood plasma cells of acute HIV-1-infected individuals are predominantly targeted to the HIV Env gp41 and cross-reactive with commensal bacteria. To understand this phenomenon, we examined anti-HIV responses in ileum B cells using recombinant antibody technology and probed their relationship to commensal bacteria. The dominant ileum B cell response was to Env gp41. Remarkably, a majority (82%) of the ileum anti-gp41 antibodies cross-reacted with commensal bacteria, and of those, 43% showed non-HIV-1 antigen polyreactivity. Pyrosequencing revealed shared HIV-1 antibody clonal lineages between ileum and blood. Mutated immunoglobulin G antibodies cross-reactive with both Env gp41 and microbiota could also be isolated from the ileum of HIV-1 uninfected individuals. Thus, the gp41 commensal bacterial antigen cross-reactive antibodies originate in the intestine, and the gp41 Env response in HIV-1 infection can be derived from a preinfection memory B cell pool triggered by commensal bacteria that cross-react with Env.Antibody SpecificityAntigens, BacterialCross ReactionsHIV AntibodiesHIV Envelope Protein gp41HIV InfectionsHIV-1HumansIleumMicrobiotaMolecular Sequence DataPlasma CellsProtein BindingJournal article1934-6069