Tromsø Research Foundation Starting Grant " iT cell defense in fish (iTD)" (2018-2020).

Project leader: Dr. Eva-Stina Edholm                                                                           

The team: Steingrim Svenning (senior engineer) and Agata Gondek (PhD student)

A major challenge facing the growing fish farm industry is the spread of viral diseases. To date, the most important prophylactic effort in the Norwegian aquaculture industry is vaccination. However, current vaccines, which are largely based on inactivated pathogens, fail to provide optimal protection in the field. Although fish possess immune systems resembling those seen in mammals, the organization of teleost fish (e.g. salmonid) immune systems and its T cell compartments differ in a number of fundamental aspects. Teleost fish rely heavily on their innate immune responses to overcome pathogenic threats. Thus, to optimize vaccination strategies, it is critical to harness both adaptive and innate immune cells that can assist the expansion of antigen-specific memory B and T cell pools. Notably, unconventional T cells and Natural Killer cells (NK) represent an important, largely overlooked innate immune cell population that could be targeted towards improving the elicited immune response. Thus, we study Atlantic salmon unconventional T cells, their distribution, regulation and the quantity and quality of their activation after viral challenge with the goal of improving fish vaccines.

To recognize antigens and become activated T cells rely on interaction with distinct surface molecules called Major Histocompatibility Complex (MHC) molecules . These MHC molecules come in various forms, including MHC class I and MHC class I-like molecules. Throughout evolution all jawed vertebrates express classical MHC class I genes. Jawed vertebrates also have variable numbers of heterogeneous MHC class I-like genes that encode molecules structurally similar to class I but usually with more limited tissue distribution and lower polymorphism. In mammals and amphibians certain MHC class I-like genes are critically involved in the differentiation and function of distinct subsets of unconventional T cells.  In bony fish five different MHC class I lineages have been described U, Z, S, L, and P and we are interested in understanding the function of these different MHC class I-like molecules in the immune response, specifically the potential role of these molecules as regulators of unconventional T cells.