Title: Diversity of the Immune Receptor KIR2DL3 and Implications for Bone Marrow Transplants
Abstract: Acute Myelogenous Leukemia (AML) is a deadly cancer that is treated with hematopoietic stem cell transplants (HSCT); it has relapse rates of approximately 40%. Understanding Natural Killer (NK) cells, a component of the innate immune system, is essential for decreasing these high relapse rates. This study examines how different killer immunoglobulin-like receptor (KIR) 2DL3 alleles impact the tumoral killing capacity of NK cells. To determine the effects of various KIR2DL3 alleles, my research focuses on the clinical outcomes of leukemia patients receiving HSCT. My research also determines the mechanism that is responsible for changing the effects between these KIR2DL3 alleles. I observe the differences in the percentage of expression and the cell surface expression and examine how these differences impact NK cell licensing and responsiveness. These differences are determined through flow cytometry. My findings show that the KIR2DL3*005 allele increases the probability of relapse for leukemia patients post-transplant. This suggests that screening for these alleles prior to transplantation, through the genotyping method we developed, is a viable and potentially effective strategy for decreasing relapse rates. My research also shows that the differences in expression impact the tumoral killing capabilities of NK cells. In addition, by determining the mechanism for the observed results, I present a potential strategy for future drug development.