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Camel heavy‐chain antibodies: diverse germline V H H and specific mechanisms enlarge the antigen‐binding repertoire
Author(s) -
Nguyen Viet Khong,
Hamers Raymond,
Wyns Lode,
Muyldermans Serge
Publication year - 2000
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/19.5.921
Subject(s) - somatic hypermutation , biology , germline , hypervariable region , microbiology and biotechnology , genetics , antigen , complementarity determining region , immunoglobulin light chain , gene , germline mutation , antibody , mutation , b cell
The antigen‐binding site of the camel heavy‐chain antibodies devoid of light chain consists of a single variable domain (V H H) that obviously lacks the V H –V L combinatorial diversity. To evaluate the extent of the V H H antigen‐binding repertoire, a germline database was constructed from PCR‐amplified V H H/V H segments of a single specimen of Camelus dromedarius . A total of 33 V H H and 39 VH unique sequences were identified, encoded by 42 and 50 different genes, respectively. Sequence comparison indicates that the V H H s evolved within the V H subgroup III. Nevertheless, the V H H germline segments are highly diverse, leading to a broad structural repertoire of the antigen‐binding loops. Seven V H H subfamilies were recognized, of which five were confirmed to be expressed in vivo . Comparison of germline and cDNA sequences demonstrates that the rearranged V H H s 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 V H H germline genes at the regions affecting the structure of the antigen‐binding loops.