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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2010-7-29
pubmed:abstractText
The power of the adaptive immune system to identify novel antigens depends on the ability of lymphocytes to create antigen receptors with diverse antigen-binding sites. For immunoglobulins, CDR (complementarity-determining region)-H3 lies at the center of the antigen-binding site, where it often plays a key role in antigen binding. It is created de novo by VDJ rearrangement and is thus the focus for rearrangement-dependent diversity. CDR-H3 is biased for the inclusion of tyrosine. In seeking to identify the mechanisms controlling CDR-H3 amino acid content, we observed that the coding sequence of DH gene segments demonstrate conservation of reading frame (RF)-specific sequence motifs, with RF1 enriched for tyrosine and depleted of hydrophobic and charged amino acids. Use of DH RF1 in functional VDJ transcripts is preferred from the earliest stages of B-cell development, "pushing" CDR-H3 to include specific categories of tyrosine-enriched antigen-binding sites. With development and maturation, the composition of the CDR-H3 repertoire appears to be pulled into a more refined specific range. Forcing the use of alternative DH RFs by means of gene targeting alters the expressed repertoire, enriching alternative sequence categories. This change in the repertoire variably affects antibody production and the development of specific B-cell subsets.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1040-8401
pubmed:author
pubmed:issnType
Print
pubmed:volume
30
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
327-44
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Genetic control of DH reading frame and its effect on B-cell development and antigen-specifc antibody production.
pubmed:affiliation
Department of Medicine, University of Alabama at Birmingham, 35294-2182, USA. hwsj@uab.edu
pubmed:publicationType
Journal Article, Review