Cunningham Group - Comparative Immunology
(September 1998 - September 2003)
Evidence obtained from a wide variety of species suggests that immunoglobulins, T cell receptors and major histocompatibility complex (MHC) molecules are present in all vertebrates including bony fish and elasmobranchs (sharks and rays). In contrast, these molecules appear to be absent from agnathans (a sister group to vertebrates) and invertebrates. Similarly, it is likely that while vertebrates possess a wide variety of immune cell types and a complex molecular signalling network of cytokines and receptors to coordinate and control immune responses, the degree of complexity in invertebrates is likely to be less pronounced. The major aim of the comparative immunology group is to understand how the complex vertebrate immune system evolved from its invertebrate counterpart. To this end we are studying groups of MHC related genes which have co-evolved and individual genes which have are either been proven to exist, or are thought to exist in higher invertebrates and agnathans.
Vertebrate genomes contain regions which are paralogous to the MHC. Paralogous genes within the same species are descended from the same ancestral gene by duplication and divergence during evolution. It has been proposed that the MHC arose as a result of ancient chromosomal duplications that took place in a common ancestor of the vertebrates. We are studying the nature of these paralogs in agnathan hagfish to determine how the vertebrate paralogs evolved and to determine if a primitive MHC gene exists within the invertebrate paralogs. Individual genes being studied in agnathans include those encoding (1) transcription factors involved in the differentiation of immune cell repertoires; (2) the SWAP-70 gene, which has been shown in vertebrates to play a central role in immunoglobulin class switching and (3) the genes encoding TGFb and interleukin 1 family members. Knowledge derived from these studies will not only inform us about the nature and complexity of the agnathan immune system, it will also provide information which will help us to understand the evolution of vertebrate immunity.