33-OR

Abstract

Natural killer cells (NKC) express many different cell surface receptors including KIR. KIR genes recognize polymorphic HLA class I including HLA-A, B & C allotypes. The KIR genes after binding specific ligands may transmit inhibitory or activating signals. NKC sense & kill target cells lacking MHC class I molecules & release various cytokines on activation. UCB is an increasingly used source of HSC for pts without matched adult donor for Tx. The goal of the study was to attain frequencies (freq) of HLA-L in UCBU aimed at providing information (info) for finding UCB with NK benefit for HSC Tx pts. Total of 21,002 UCBU from Cord Bank at MD Anderson was included. HLA typing of class I & II loci were obtained using PCR/probe based methods & sequence-based typing as needed. Freq of Bw4 alleles, C1 and C2 HLA-C alleles were obtained. KIR3DL1 recognizes allotypes with HLA-Bw4 serological motif; KIR2DL1 recognizes HLA-C allotypes with lysine at codon 80 (group 2 - C2); & KIR2DL2/KIR2DL3 recognize C alleles with asparagine at residue 80 (group 1 - C1). Among the 21,002 UCBU, 70.7% carry Bw4 alleles. UCB bearing C1/C2 heterozygous genotype (GT) accounted for 45.6%, C1/C1 homozygous GT for 39.6%, & C2/C2 GT for 14.7% only. Incompatibility of KIR HLA-L between pt & donor has been shown to impact graft outcome (GO) in HSC Tx. NKC from the donor greatly contribute to eradication of leukemia blasts escaping the preparative regimen & to clearance of residual host dendritic cells & T lymphocytes thus preventing graft-versus-host disease & graft rejection. This study showed high freq of Bw4-bearing GT, increased freq of C1/C2, & C1/C1 but not C2/C2 GT in UCBU. These freq info could be useful for prediction of the possibility for HSC Tx pts, especially those with Bw6 or C2/C2 GT, to find suitable UCB donor(s) with beneficial NK reactivity, thereby improving GO. Further study of diversification of KIR HLA-ligands in pts would be warranted to assess the importance of these findings.