Design principles of adaptive immune systems

Key Points Both jawless vertebrates, such as lampreys and hagfish, and jawed vertebrates (encompassing species as diverse as sharks and humans) possess T-like and B-like lymphocytes. Jawless vertebrates use variable lymphocyte receptors (VLRs) consisting of leucine-rich repeats whereas jawed vertebrates rely on antigen receptors of the immunoglobulin superfamily, such as immunoglobulins and T cell receptors (TCRs). All vertebrates use somatic diversification to generate highly diverse repertoires of antigen receptors. Jawless vertebrates diversify their VLR genes by a process akin to gene conversion, whereas the diversification of immunoglobulin and TCR genes is achieved by the process of V(D)J recombination. T-like cells develop in the thymoids of lampreys and the thymus of jawed vertebrates, whereas B cells develop in anatomically distinct haematopoietic tissues. The astounding sequence diversity of the VLRA receptors expressed by T-like cells of lampreys suggests that mechanisms exist to tame potential self-reactivity; the search for an MHC equivalent is one of the priorities in the study of cellular immunity in jawless vertebrates.