Linked Life Data

12921758

Source:http://linkedlifedata.com/resource/pubmed/id/12921758

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2003-8-18
pubmed:abstractText
A structurally conserved antibody combining site, encoded by the IGH V3-23 and kappa A2 variable (V) region gene segments, predominates the adult immune response to the Haemophilus influenzae type b (Hib) capsular polysaccharide (PS). This site has been elevated to canonical status based upon its relative molecular uniformity and prevalence in adults. To date, no studies have examined the primary structure of Hib PS-specific antibodies in young infants, who are the primary targets of Hib vaccination. In this study we show that canonical Hib PS-specific heavy (H) and light (L) chain V regions are present in 4-month-old infants following two vaccinations with Hib PS-protein conjugates. The infant V regions contain sequence polymorphisms that resemble those found in adult antibodies, as well as polymorphisms at position 95a of the A2 L chain not previously observed in adults. In vitro studies of Fab fragments and recombinant IgG2 antibodies using these V regions identify sequence polymorphisms that impact Hib PS binding affinity and bactericidal activity. These results demonstrate the establishment of canonical V regions in early ontogeny and provide a structural explanation of how canonical antibodies in the infant can vary in their affinity and protective activity against Hib.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies, Anti-Idiotypic, http://linkedlifedata.com/resource/pubmed/chemical/Antibodies, Bacterial, http://linkedlifedata.com/resource/pubmed/chemical/Bacterial Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Haemophilus Vaccines, http://linkedlifedata.com/resource/pubmed/chemical/HibTITER protein, Haemophilus..., http://linkedlifedata.com/resource/pubmed/chemical/Immunoglobulin Fab Fragments, http://linkedlifedata.com/resource/pubmed/chemical/Immunoglobulin Heavy Chains, http://linkedlifedata.com/resource/pubmed/chemical/Immunoglobulin Light Chains, http://linkedlifedata.com/resource/pubmed/chemical/Immunoglobulin Variable Region, http://linkedlifedata.com/resource/pubmed/chemical/Polysaccharides, Bacterial, http://linkedlifedata.com/resource/pubmed/chemical/Vaccines, Synthetic
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1521-6616
pubmed:author
pubmed:issnType
Print
pubmed:volume
108
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
119-27
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:12921758-Amino Acid Sequence, pubmed-meshheading:12921758-Antibodies, Anti-Idiotypic, pubmed-meshheading:12921758-Antibodies, Bacterial, pubmed-meshheading:12921758-Bacterial Proteins, pubmed-meshheading:12921758-Base Sequence, pubmed-meshheading:12921758-Haemophilus Infections, pubmed-meshheading:12921758-Haemophilus Vaccines, pubmed-meshheading:12921758-Haemophilus influenzae type b, pubmed-meshheading:12921758-Humans, pubmed-meshheading:12921758-Immunoglobulin Fab Fragments, pubmed-meshheading:12921758-Immunoglobulin Heavy Chains, pubmed-meshheading:12921758-Immunoglobulin Light Chains, pubmed-meshheading:12921758-Immunoglobulin Variable Region, pubmed-meshheading:12921758-Infant, pubmed-meshheading:12921758-Molecular Sequence Data, pubmed-meshheading:12921758-Polymorphism, Genetic, pubmed-meshheading:12921758-Polysaccharides, Bacterial, pubmed-meshheading:12921758-Sequence Homology, Nucleic Acid, pubmed-meshheading:12921758-Vaccination, pubmed-meshheading:12921758-Vaccines, Synthetic
pubmed:year
2003
pubmed:articleTitle
Molecular ontogeny of the human antibody repertoire to the Haemophilus influenzae type B polysaccharide: expression of canonical variable regions and their variants in vaccinated infants.
pubmed:affiliation
Children's Hospital Oakland Research Institute, Oakland, CA 94609, USA. alucas@chori.org
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S.