1. A novel promiscuous class of camelid single-domain antibody contributes to the antigen-binding repertoire.
- Author
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Deschacht N, De Groeve K, Vincke C, Raes G, De Baetselier P, and Muyldermans S
- Subjects
- Animals, Bone Marrow Cells immunology, Bone Marrow Cells metabolism, Cells, Cultured, Female, Humans, Immunoglobulin Fab Fragments metabolism, Mice, Mice, Inbred C57BL, Protein Structure, Tertiary, Antigens metabolism, Binding Sites, Antibody immunology, Camelids, New World immunology, Camelus immunology, Immunoglobulin Heavy Chains metabolism, Immunoglobulin Variable Region metabolism
- Abstract
It is well established that, in addition to conventional Abs, camelids (such as Camelus dromedarius and Lama glama) possess unique homodimeric H chain Abs (HCAbs) devoid of L chains. The Ag-binding site of these HCAbs consists of a single variable domain, referred to as VHH. It is widely accepted that these VHHs, with distinct framework-2 imprints evolved within the V(H) clan III-family 3, are exclusively present on HCAbs. In this study, we report the finding of a distinct leader signal sequence linked to variable genes displaying a high degree of homology to the clan II, human VH(4) family that contributes to the HCAb Ag-binding diversity. Although the VHH framework-2 imprints are clearly absent, their VH(4)-D-JH recombination products can be rearranged to the H chains of both classical and HCAbs. This suggests that for these V domains the presence of a L chain to constitute the Ag-binding site is entirely optional. As such, the capacity of this promiscuous VH(4) family to participate in two distinct Ab formats significantly contributes to the breadth of the camelid Ag-binding repertoire. This was illustrated by the isolation of stable, dendritic cell-specific VH(4) single domains from a VH(4)-HCAb phage display library. The high degree of homology with human VH(4) sequences is promising in that it may circumvent the need for "humanization" of such single-domain Abs in therapeutic applications.
- Published
- 2010
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