CHARACTERIZATION OF THE MOST EVOLUTIONARILY CONSERVED NATURAL KILLER RECEPTOR, NKp30, IN EARLY VERTEBRATES
Yuko Ota, University of Maryland
Yuko Ohta, Martin F. Flajnik
Department of Microniology and Immunology, University of Maryland, Baltimore, Maryland
Natural killer receptors (NKR) are among the most rapidly evolving immune-recognition molecules. It is assumed that NKR continually undergo modifications to combat ever-changing viruses, and thus orthologous receptors are rarely detected among different vertebrate classes. In stark contrast to this paradigm, we identified NKp30 genes from amphibians and sharks (human NKp30 was found previously), revealing that NKp30 is the most conserved and oldest NKR. The NKp30 gene in all vertebrates has a unique variable V-type domain resembling the precursor of antigen receptors (AgR), and thus likely predates the emergence of AgR. Sharks are the oldest living jawed vertebrates possessing an immune system similar to mammals, and therefore provide an excellent comparative model. In the nurse shark bacterial artificial chromosomes (BAC) clones spanning 300kbp, we identified nine NKp30 genes with at least 5 different subtypes containing divergent V-type. Our preliminary results suggest that NKp30 is linked to the major histocompatibility complex (MHC) in sharks. These observations support the hypothesis that AgR/NKR and MHC genes were syntenic early in vertebrate evolution. Moreover, shark NK cells were previously identified, however they were not characterized at the molecular level. In order to characterize NKp30-expressing NK cells, we generated polyclonal antisera against the highest expressed shark NKp30, and found that the NKp30 is also expressed by shark T cells. As NK and T cells are crucial for cellular immunity and are likely derived from a common “killer cell” precursor, NKp30 might be a common marker for both cell types in early vertebrates.