My work is centered on the evolution of the immune system, with the major goal being to understand the origins of adaptive immunity. The laboratory employs a holistic approach, using all existing methods to investigate this problem. The adaptive immune system is defined by antigen receptors of great diversity < immunoglobulin (Ig) and T cell receptors (TCR) < and by molecules encoded in the major histocompatibility complex (MHC) that present foreign antigens for T cell recognition. In addition, the adaptive immune system is contrasted to the non-adaptive or innate immune system by displaying: i) great diversity of the antigen-receptor repertoire; ii) specific and augmented memory responses; and iii) epigenetically determined self tolerance. We believe that evolutionary studies permit a judgment of those structures and mechanisms vital for a functioning immune system and reveal other phenomena that have arisen to fulfill specific functions in particular taxonomic lineages. The adaptive immune system so far has been identified only in jawed vertebrates, including the cartilaginous fish (e.g. sharks and skates), bony fish (e.g. trout, zebrafish), amphibians (e.g. Xenopus), reptiles, birds, and mammals. Our work (and that of other labs) has shown that the oldest group, the cartilaginous fish, while exhibiting an unusual immune system in which specific antibody responses do not increase in quality over time, nevertheless possess all of the building blocks of an adaptive immune system. We hope to build on these studies to identify related genes/mechanisms in more ancient groups of organisms that do not possess a true adaptive immune system.