NDLI: Camel heavy-chain antibodies: diverse germline VHH and specific mechanisms enlarge the antigen-binding repertoire

Content Provider	PubMed Central
Author	Nguyen, Viet Khong Hamers, Raymond Wyns, Lode Serge, Muyldermans
Copyright Year	2000
Abstract	The antigen-binding site of the camel heavy-chain antibodies devoid of light chain consists of a single variable domain (VHH) that obviously lacks the VH–VL combinatorial diversity. To evaluate the extent of the VHH antigen-binding repertoire, a germline database was constructed from PCR-amplified VHH/VH segments of a single specimen of Camelus dromedarius. A total of 33 VHH and 39 VH unique sequences were identified, encoded by 42 and 50 different genes, respectively. Sequence comparison indicates that the VHHs evolved within the VH subgroup III. Nevertheless, the VHH germline segments are highly diverse, leading to a broad structural repertoire of the antigen-binding loops. Seven VHH subfamilies were recognized, of which five were confirmed to be expressed in vivo. Comparison of germline and cDNA sequences demonstrates that the rearranged VHHs are extensively diversified by somatic mutation processes, leading to an additional hypervariable region and a high incidence of nucleotide insertions or deletions. These diversification processes are driven by hypermutation and recombination hotspots embedded in the VHH germline genes at the regions affecting the structure of the antigen-binding loops.
Related Links	http://dx.doi.org/10.1093/emboj/19.5.921
Ending Page	930
Page Count	10
Starting Page	921
File Format	PDF
ISSN	02614189
e-ISSN	14602075
Journal	The EMBO Journal
Issue Number	5
Volume Number	19
Language	English
Publisher	Oxford University Press
Publisher Date	2000-03-01
Access Restriction	Open
Rights Holder	Oxford University Press
Subject Keyword	Biochemistry, Genetics and Molecular Biology(all) Immunology and Microbiology(all) Neuroscience(all) Molecular Biology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Neuroscience Immunology and Microbiology Medicine Molecular Biology

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