P053 : DISTRIBUTION OF KIR HLA LIGANDS IN TRANSPLANT PATIENTS AND THEIR CORD BLOOD UNIT (CBU) DONORS

Abstract

Aim Killer cell immunoglobulin-like receptor (KIR) genes are receptors expressed on the surface of natural killer cells. KIR genes recognize polymorphic epitopes of HLA class I-A, B & C, called KIR HLA ligands (HLA-L). After binding specific ligands the KIR may transmit inhibitory or activating signals. NKC sense & kill target cells missing MHC class I molecules. Studies showed that hematopoietic stem cells (HSC) transplant patients may benefit from NK alloreactivity of the donor or HLA-C alleles (C1/x) of the recipients. Previously we reported the diversification of KIR HLA-L in CBU from MD Anderson Cord Bank. The goal of this study was to further explore the frequency (Freq) of HLA-L in selected CBU from the bank and their transplant recipients aimed at providing information for finding the best donor and improving graft outcome. Methods 640 CBU selected from MD Anderson Cord Bank and 589 recipients were included. HLA typing of class I & II loci were obtained using PCR/probe based methods & sequence-based typing as needed. Freq of Bw4, C1, and C2 group of HLA-C alleles were examined. Results KIR3DL1 recognizes allotypes with HLA-Bw4 motif; KIR2DL1 recognizes HLA-C epitope with lysine at codon 80 (group 2-C2); while KIR2DL2 and KIR2DL3 recognize C alleles with asparagine at residue 80 (group 1-C1). Among the 640 CBU and 589 recipients, 70.0% and 72.0%, respectively, carry Bw4 bearing phenotypes. HLA-C1 bearing phenotypes (C1/x) were found to be predominated in both CBU (85.2%) and their transplant recipients(81.5%). Missing HLA-C1 was lower (C2/C2, 18.5%) than missing C2 (C1/C1, 33.1%) in recipients (Table 1). Conclusion Here we show that CBU can be classified based on their KIR repertoire (licensed versus unlicensed) and the presence of KIR-ligand mismatch with the recipient. Analysis of graft outcome in these HSC transplant recipients is underway. The ultimate goal of our study is to develop algorithms based on the KIR profile of CB units to select the units with maximum antileukemic activity to improve the outcome of CBU transplant.