Llama Single Domain Antibodies as a Tool for Molecular Mimicry

In camelids, a subset of the immunoglobulins consists of heavy-chain homodimers devoid of light chains, and are thus called heavy-chain IgGs (hcIgGs). Their variable region (VHH) is the smallest antigen-binding fragment possible, and being just one polypeptide chain it is especially suitable for engineering. In particular, camelid single domain antibodies might be very useful for molecular mimicry and anti-idiotypic vaccination. In the present work, we show that llamas immunized with an anti-DNA mouse mAb develop an important anti-Id response. Selection of VHHs by phage display, with specific elution of bound phages with the external antigenic DNA, shows that selected private anti-Id VHHs compete for binding to the external antigen and bear a functional mimicry of the DNA. These results indicate that llama anti-Id single domain antibodies would be an excellent tool for molecular mimicry studies.