The natural cytotoxicity receptor NKp44 (NCR2, CD336) is expressed on the majority of porcine NK cells ex vivo without stimulation

Authors: MAIR, KH - University Of Veterinary Medicine; CROSSMAN, AJ - Non ARS Employee; WAGNER, BETTINA - Cornell University; BABSYAN, S - Cornell University; NORONHA, L - Non ARS Employee; BOYD, P - Retired ARS Employee; Zarlenga, Dante; STADLER, M - University Of Veterinary Medicine; VON DONGEN, KA - University Of Veterinary Medicine; GERNER, W - University Of Veterinary Medicine; SALLMUELLER, A - University Of Veterinary Medicine; Lunney, Joan

Submitted to: Frontiers in Immunology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/10/2022
Publication Date: 1/28/2022
Citation: Mair, K., Crossman, A., Wagner, B., Babsyan, S., Noronha, L., Boyd, P., Zarlenga, D.S., Stadler, M., Von Dongen, K., Gerner, W., Sallmueller, A., Lunney, J.K. 2022. The natural cytotoxicity receptor NKp44 (NCR2, CD336) is expressed on the majority of porcine NK cells ex vivo without stimulation. Frontiers in Immunology. https://doi.org/10.3389/fimmu.2022.767530.
DOI: https://doi.org/10.3389/fimmu.2022.767530

Interpretive Summary: Natural killer (NK) cells, cells stimulate important innate immune responses in mammals, but their function was poorly understood in pigs. We therefore produced and characterized a monoclonal antibody that binds a marker of these cells. We used this new tool to determine this marker’s expression patterns. Whereas expression in the NK cells of mice and humans requires stimulation, expression in in pigs does not. This new antibody will greatly aid efforts to elucidate differentiation, function, and activation of porcine NK cells. It will expand our understanding of their role in pig immune development and disease responses. Adding “tools to the toolkit” aid basic and applied research understand and improve pig immune responses disease vaccination, aiding pork producers, veterinarians, pharmaceutical and breeding companies, and the general public who require a safe and affordable food supply.

Technical Abstract: Natural killer (NK) cells have been studied extensively in humans and mice for their vital role in the vertebrate innate immune system. They mobilize lytic immune responses that rapidly eliminate tumors and virus-infected cells. The natural cytotoxicity receptors (NCRs) NKp30 (NCR3), NKp44 (NCR2), and NKp46 (NCR1) are important mediators of NK-cell cytotoxicity. Only activated NK cells in humans and certain other primates express NKp44. Understanding the expression and role of NKp44 in porcine lymphocytes required specific monoclonal antibodies(mAbs). We therefore purified and tested such antibodies on various NK cells derived from various pig tissues in animals of varying age. Interestingly, we detected NKp44 expression ex vivo in resting NK cells; moreover, NKp44 was more abundant than NKp46. In vitro stimulation with IL-2 or IL-15 increased the frequency of NKp44+ NK cells and the amount of NKp44 each of those cells expressed. A monoclonal antibody against NKp44(clone 54-1) will greatly aid efforts to elucidate mechanisms underlying NK cell differentiation, function, and activation in swine. This information will benefit immunologists, veterinarians, swine breeders and producers.