Unique aspects of adaptive immunity in camelids and their applications

Members of the Camelidae have unique adaptive immunological features that are not widely observed in other species. All camelids are known to have three distinct IgG isotypes - IgG1, IgG2 and IgG3. While IgG1 has a conventional antibody structure, both IgG2 and IgG3 are devoid of light chains and instead possess hypervariable regions in their heavy chain (VHH), while lacking the typical CH1 domain found in heavy chains. VHH domains are increasingly being utilized as "next generation" antibodies, as they have unique biochemical and structural properties including high pH stability as well as a lower molecular weight allowing for increased tissue penetration. These features of VHH domains offer a number of advantages for both biotechnology and clinical applications and are commonly termed "nanobodies". A second unique aspect of the camelid adaptive response is involves T cell-mediated immunity. Characterization of gamma delta (ꝩδ) T cells in camelid species has found they use somatic hypermutation in their T cell receptor gamma (TRG) and delta (TRD) loci to increase the structural stability of their ꝩδ T receptor. The use of somatic hyper mutation to increase the diversity of their T cell repertoire, is a feature that has not been observed in other mammalian species. In addition, in alpacas there is a unique subset of ꝩδ T cells called Vꝩ9Vδ2 T cells. Activation of these cells is dependent upon phosphoantigen (PAg)-mediated interaction with B7-like butyrophilin molecules (BTN-3). This makes alpacas the first species outside of primates to be identified with this unique subset and activation mechanism. Here we review some fundamentals of camelid adaptive immunity that make them distinct from other vertebrate species and their potential applications to human therapies.