Single domain antibody, also known as domain antibody, V_HH, V_NAR or sdAb, is a kind of antibody fragments consisting of a single monomeric variable antibody domain and lacking the light chain and CH domain of the heavy chain in conventional Fab region. Single domain antibodies are found in different species, such as V_HH in camelids, V_NAR in cartilaginous fishes and VLR in lampreys.

V_HH from Camelid

By serendipity, a new kind of functional homodimeric antibody format has been discovered in all camelid, known as heavy-chain antibodies (HCAbs), which naturally lack light chains and constant heavy chain 1 (CH1) domain in the heavy chain. These HCAbs have an antigen-binding part composed of single variable domains, referred to as the variable domain of the heavy chain of heavy-chain antibody (V_HH), or also named as single domain antibody (sdAb). This V_HH is currently the smallest naturally derived antigen-binding fragment. Although sdAbs with a molecular weight of 12-15 kDa are much smaller than monoclonal antibodies or even engineered antibody fragments, they exhibit specificities and affinities comparable to that of conventional antibodies. We will describe sdAb in more details, including the following aspects:

• Introduction to heavy-chain only antibody and derived single domain antibody
• From whole monoclonal antibody to single domain antibody
• Single domain antibody VS conventional antibody
• Considerations of Animal Selection During Single Domain Antibody Development

Fig.1 V_HH from Camelid.

V_NAR from Shark

Besides antibody with the classical composition of heavy and light chains, the immune system of shark comprises a distinct class of heavy-chain only antibody (HCAb), which is called immunoglobulin new antigen receptor (IgNAR), consisting of homodimers with no associated light chains. The antigen-binding site of heavy-chain antibodies is mediated solely by one single domain, referred to variable domain of new antigen receptor (V_NAR) for sharks. The V_NAR is the smallest intact antigen-binding domain derived from the IgNAR naturally occurring in cartilaginous fish. Please visit the overview & discovery of IgNARs and generation of V_NARs for more detailed information about V_NAR.

Fig.2 V_NAR from shark.

VLR from Lamprey

Lamprey is the representative of primitive jawless vertebrates capable of mounting specific adaptive immune responses. Lamprey lacking T-cell and B-cell receptors possesses lymphocyte-like cells (LLCs) that clonally express somatically diversified unique antigen receptor termed variable lymphocyte receptor (VLR), the oldest adaptive immune receptor, which is consisted of tandem arrays of leucine-rich repeat (LRR) modules. The high affinity of matured VLR makes it a potential alternative to conventional antibodies for biotechnology applications. More details about VLR from lamprey are described in the overview & discovery of VLRs in lamprey.

Fig.3 VLR from lamprey

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