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First molecular and biochemical analysis ofin vivoaffinity maturation in an ectothermic vertebrate
- Source :
- Proceedings of the National Academy of Sciences. 103:1846-1851
- Publication Year :
- 2006
- Publisher :
- Proceedings of the National Academy of Sciences, 2006.
-
Abstract
- The cartilaginous fish are the oldest phylogenetic group in which Igs have been found. Sharks produce a unique Ig isotype, IgNAR, a heavy-chain homodimer that does not associate with light chains. Instead, the variable (V) regions of IgNAR bind antigen as soluble single domains. Our group has shown that IgNAR plays an integral part in the humoral response of nurse sharks (Ginglymostoma cirratum) upon antigen challenge. Here, we generated phage-displayed libraries of IgNAR V regions from an immunized animal and found a family of clones derived from the same rearrangement event but differentially mutated during expansion. Because of the cluster organization of shark Ig genes and the paucicopy nature of IgNAR, we were able to construct the putative ancestor of this family. By studying mutations in the context of clone affinities, we found evidence that affinity maturation occurs for this isotype. Subsequently, we were able to identify mutations important in the affinity improvement of this family. Because the family clones were all obtained after immunization, they provide insight into thein vivomaturation mechanisms, in general, and for single-domain antibody fragments.
- Subjects :
- Fish Proteins
Models, Molecular
Genetics
Multidisciplinary
Molecular Sequence Data
Sequence alignment
Context (language use)
Biological Sciences
Biology
Immunoglobulin light chain
Isotype
Body Temperature
Protein Structure, Tertiary
Affinity maturation
Germ Cells
Antigen
Sharks
Animals
Amino Acid Sequence
Clone (B-cell biology)
Sequence Alignment
Gene
Body Temperature Regulation
Subjects
Details
- ISSN :
- 10916490 and 00278424
- Volume :
- 103
- Database :
- OpenAIRE
- Journal :
- Proceedings of the National Academy of Sciences
- Accession number :
- edsair.doi.dedup.....793b696bb3bc38943eacd5b56c5fca06