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We have now generated and characterized three <jats:styled-content style=\"fixed-case\">mA<\/jats:styled-content>bs specific for the non\u2010reducing end of <jats:italic><jats:styled-content style=\"fixed-case\">F<\/jats:styled-content>.\u00a0tularensis <\/jats:italic><jats:styled-content style=\"fixed-case\">OA<\/jats:styled-content>g, partially encoded by the same variable region germline genes, indicating that they target the same epitope. Like FB11, the new <jats:styled-content style=\"fixed-case\">mA<\/jats:styled-content>bs, <jats:styled-content style=\"fixed-case\">A<\/jats:styled-content>b63 (Ig<jats:styled-content style=\"fixed-case\">G<\/jats:styled-content>3), N213 (Ig<jats:styled-content style=\"fixed-case\">G<\/jats:styled-content>3) and <jats:styled-content style=\"fixed-case\">N<\/jats:styled-content>62 (Ig<jats:styled-content style=\"fixed-case\">G<\/jats:styled-content>2b), had higher antigen\u2010binding bivalent avidity than internally binding anti\u2010<jats:styled-content style=\"fixed-case\">OA<\/jats:styled-content>g <jats:styled-content style=\"fixed-case\">mA<\/jats:styled-content>bs, and an oligosaccharide containing a single <jats:styled-content style=\"fixed-case\">OA<\/jats:styled-content>g repeat was sufficient for optimal inhibition of their antigen\u2010binding. The <jats:styled-content style=\"fixed-case\">X<\/jats:styled-content>\u2010ray crystal structure of <jats:styled-content style=\"fixed-case\">N<\/jats:styled-content>62 Fab showed that the antigen\u2010binding site is lined mainly by aromatic amino acids that form a small cavity, which can accommodate no more than one and a third sugar residues, indicating that N62 binds mainly to the terminal Qui4<jats:styled-content style=\"fixed-case\">NF<\/jats:styled-content>m residue at the nonreducing end of <jats:styled-content style=\"fixed-case\">OA<\/jats:styled-content>g. In efficacy studies with mice infected intranasally with the highly virulent <jats:italic><jats:styled-content style=\"fixed-case\">F<\/jats:styled-content>.\u00a0tularensis<\/jats:italic> strain <jats:styled-content style=\"fixed-case\">S<\/jats:styled-content>chu<jats:styled-content style=\"fixed-case\">S<\/jats:styled-content>4, <jats:styled-content style=\"fixed-case\">N<\/jats:styled-content>62, <jats:styled-content style=\"fixed-case\">N<\/jats:styled-content>213 and <jats:styled-content style=\"fixed-case\">A<\/jats:styled-content>b63 prolonged survival and reduced blood bacterial burden. These results yield insights into how antibodies to non\u2010reducing ends of microbial polysaccharides can contribute to immune protection despite the smaller size of their target epitopes compared with antibodies to internal polysaccharide regions.<\/jats:p>","DOI":"10.1111\/imm.12150","type":"journal-article","created":{"date-parts":[[2013,7,11]],"date-time":"2013-07-11T14:08:21Z","timestamp":1373551701000},"page":"374-389","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["The binding sites of monoclonal antibodies to the non\u2010reducing end of <i><scp>F<\/scp>rancisella tularensis <scp>O<\/scp><\/i>\u2010antigen accommodate mainly the terminal saccharide"],"prefix":"10.1111","volume":"140","author":[{"given":"Zhaohua","family":"Lu","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Boston University School of Medicine Boston MA 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