|Title||A novel promiscuous class of camelid single-domain antibody contributes to the antigen-binding repertoire.|
|Publication Type||Journal Article|
|Year of Publication||2010|
|Authors||Deschacht, N., K. De Groeve, C. Vincke, G. Raes, P. De Baetselier, and S. Muyldermans|
|Date Published||2010 May 15|
|Keywords||Animals, Antigens, Binding Sites, Antibody, Bone Marrow Cells, Camelids, New World, Camels, Cells, Cultured, Female, Humans, Immunoglobulin Fab Fragments, Immunoglobulin Heavy Chains, Immunoglobulin Variable Region, Mice, Mice, Inbred C57BL, Protein Structure, Tertiary|
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.
|Alternate Journal||J. Immunol.|