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Camelid Heavy-Chain Antibodies and Single-Domain Antibodies

Research Focus

The occurrence of bona fide antibodies devoid of light chains in Camelidae was one of the major discoveries within our department. These so-called heavy-chain antibodies (HCAbs) bind antigen solely with one single variable domain, referred to as VHH. Methods were developed to clone the VHH repertoire of an immunised dromedary (or llama) in phage display vectors, and to select the antigen-specific VHHs from these 'immune' VHH libraries.
Our current research activities on camelid HCAbs and VHHs aims at three goals: (i) to increase the fundamental knowledge of VHH characteristics and HCAb ontogeny, (ii) to broaden the efficacy of VHHs and to extent their applications in medical or biotechnological fields where the unique VHH properties offer a clear advantage over other antibody formats, and (iii) to develop new VHH selection strategies that are amenable to a high throughput mode. The objective here is to arrive at a rapid identification of small molecular probes to be employed in biosensors, functional genomics, structural genomics and proteomics. Obviously, the appearance of HCAbs requires the acquisition of multiple events to allow their generation and maturation into functional molecules. The dromedary germline genes (V, D, and J) and constant immunoglobulin genes used to generate HCAbs are known. Analysis of these genes forms the cornerstone to understand the emergence and ontogeny of HCAbs in camelids. The antigen-specific VHHs we retrieve have excellent biochemical and biophysical properties (antigen affinity, specificity, solubility, stability, small size, recognition of epitopes that are less immunogenic for conventional antibodies). We obtained the crystal structure of many VHHs in complex with their antigen, and this forms the basis for a further engineering of the VHHs to develop more versatile small molecular units. These small units are used as building blocks for more complex constructs, which are being tested as probe in biosensors, to neutralise the toxins in envenomed patients, or for tumour targeting, etc.

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Selected Publications

Search all publications of S. Muyldermans on PubMed

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©2011• Cellular and Molecular Immunology • Last update of this page on 15/01/2015