#60
KIR GENETIC PROFILES IN AN NMDP DONOR AND RECIPIENT POPULATION.
Robert J. Nichols, BS, Kathleen A. Houtchens, PhD, Hannah E. Boal, BS and Elizabeth A. Trachtenberg, PhD. Oakland CA, Children
s Hospital and Research Center, HLA.
Killer cell immunoglobulin-like receptors (KIR) are molecules involved in the host natural killer (NK) cell response to viral infection and non-self antigens. Recognition of their Human Leukocyte Antigen (HLA) class I ligands leads to an inhibitory, or in some cases stimulatory, response in which NK cell cytotoxicity is either down or up-regulated. The nature of the response is dependent not only upon the NK receptor involved, but also on the presence or absence of the receptor-specific ligand. KIR-derived NK cytolytic activity may result from the binding of stimulatory receptor ligands as well as from the “missing-self” scenario in which the HLA ligand of an inhibitory receptor is absent. Recently, it has been proposed that the missing-self NK activation may be of great benefit in hematopoeitic transplants, as donor NK cells in a KIR/HLA mismatched transplant have shown the ability to attack host leukemias and reduce graft versus host disease and graft rejection. Here, we present KIR genetic profiles obtained from an NMDP population of 100 donor and recipient pairs selected to represent the ethnic diversity of the NMDP as a whole, including 84% White/Caucasian, 6% Black/African American, 6% Hispanic, and 4% Asian/Pacific Islander. Samples were amplified at four KIR domains and hybridized to 39 sequence-specific oligonucleotide (SSO) probes to ascertain genotypes with better than locus-specific resolution. The KIR genetic profiles of this population are largely heterogeneous both within and between ethnic boundaries. Similar KIR genotype analysis in HLA-typed, ethnically diverse transplant pairs will help to more fully demonstrate the heterogeneity of KIR and the proportion of the transplant population with KIR-HLA ligand mismatches.