Evolutionary biology of CD1

The recognition more than a decade ago that lipids presented by CD1 could function as T cell antigens revealed a startling and previously unappreciated complexity to the adaptive immune system. The initial novelty of lipid antigen presentation by CD1 has since given way to a broader perspective of the immune system's capacity to sense and respond to a diverse array of macromolecules. Some immune recognition systems such as Toll-like receptors can trace their origins back into the deep history of sea urchins and arthropods. Others such as the major histocompatibility complex (MHC) appear relatively recently and interestingly, only in animals that also possess a jaw. The natural history of CD1 is thus part of the wider story of immune system evolution and should be considered in this context. Most evidence indicates that CD1 probably evolved from a classical MHC class I (MHC I) gene at some point during vertebrate evolution. This chapter reviews the evidence for this phylogenetic relationship and attempts to connect CD1 to existing models of MHC evolution. This endeavor is facilitated today by the recent availability of whole genome sequence data from a variety of species. Investigators have used these data to trace the ultimate origin of the MHC to a series of whole genome duplications that occurred roughly 500 million years ago. Sequence data have also revealed homologs of the mammalian MHC I and MHC II gene families in virtually all jawed vertebrates including sharks, bony fishes, reptiles, and birds. In contrast, CD1 genes have thus far been found only in a subset of these animal groups. This pattern of CD1 occurrence in the genomes of living species suggests the emergence of CD 1 in an early terrestrial vertebrate.