title: Somatic diversity in CDR3 loops allows single V-genes to encode innate immunological memories for multiple pathogens.
abstract: The human Ab response to many common pathogens is oligoclonal, with restricted usage of Ig V-genes. Intriguingly, the IGVK3-11 and IGVH3-30 V-genes are repeatedly paired in protective Abs against the 23F polysaccharide of Streptococcus pneumoniae, as well as against the gB envelope protein of human CMV, where germline-encoded amino acids make key contacts with the gB protein. We constructed IgGs encoded by the germline IGVK3-11 and IGVH3-30 V-genes together with DNA encoding the respective CDR3 regions of the L chain and H chain found in a hypermutated anti-23F Ab. These IgGs encoded by germline V-genes bound specifically to 23F pneumococcal capsular polysaccharides with no reactivity to other serotypes of pneumococcal capsular polysaccharides or arrayed glycans and recognized L-rhamnose, a component of the 23F repeating subunit. IgGs encoded by this pair of germline V-genes mediated complement-dependent phagocytosis of encapsulated 23F S. pneumoniae by human neutrophils. Mutations in CDRL3 and CDRH3 had significant effects on binding. Thus, IGKV3-11 and IGHV3-30, depending on with which distinct DNA sequences encoding CDR3 they are recombined, can encode binding sites for protective Abs against chemically distinct Ags and thus, may encode innate immunological memory against human CMV and S. pneumoniae.
authors.affiliation: The Biomedical Research Centre, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada.
authors.forename: Christy A
authors.initials: CA
authors.lastname: Thomson
authors.forename: Ken Q
authors.initials: KQ
authors.lastname: Little
authors.forename: Donald C
authors.initials: DC
authors.lastname: Reason
authors.forename: John W
authors.initials: JW
authors.lastname: Schrader
mesh_terms: D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000378:metabolism; D001666:Binding Sites, Antibody / Q000235:genetics; D002478:Cells, Cultured; D022801:Complementarity Determining Regions / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics*; D007143:Immunoglobulin Heavy Chains / Q000235:genetics / Q000378:metabolism; D007147:Immunoglobulin Light Chains / Q000235:genetics / Q000378:metabolism; D007135:Immunoglobulin Variable Region / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D007156:Immunologic Memory / Q000235:genetics*; D008969:Molecular Sequence Data; D009504:Neutrophils / Q000276:immunology / Q000382:microbiology / Q000821:virology; D012136:Respiratory Syncytial Viruses / Q000276:immunology* / Q000378:metabolism / Q000472:pathogenicity; D027041:Somatic Hypermutation, Immunoglobulin / Q000235:genetics*; D013296:Streptococcus pneumoniae / Q000276:immunology* / Q000378:metabolism / Q000472:pathogenicity
chemical_list: D000911:Antibodies, Monoclonal; D022801:Complementarity Determining Regions; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D007135:Immunoglobulin Variable Region