%0 Journal Article
%T Role of Killer Immunoglobulin-Like Receptor and Ligand Matching in Donor Selection
%A Meral Beksa£¿
%A Klara Dalva
%J Bone Marrow Research
%D 2012
%I Hindawi Publishing Corporation
%R 10.1155/2012/271695
%X Despite all efforts to improve HLA typing and immunosuppression, it is still impossible to prevent severe graft versus host disease (GVHD) which can be fatal. GVHD is not always associated with graft versus malignancy and can prevent stem cell transplantation from reaching its goals. Overall T-cell alloreactivity is not the sole mechanism modulating the immune defense. Innate immune system has its own antigens, ligands, and mediators. The bridge between HLA and natural killer (NK) cell-mediated reactions is becoming better understood in the context of stem cell transplantation. Killer immunoglobulin-like receptors (KIRs) constitute a wide range of alleles/antigens segregated independently from the HLA alleles and classified into two major haplotypes which imprints the person's ability to suppress or to amplify T-cell alloreactivity. This paper will summarize the impact of both activating and inhibitory KIRs and their ligands on stem cell transplantation outcome. The ultimate goal is to develop algorithms based on KIR profiles to select donors with maximum antileukemic and minimum antihost effects. 1. Introduction Allogeneic hematopoietic stem cell transplantation is a curative approach. Removal of residual malignant cells and relapse prevention by an intensive conditioning regimen and reinstitution of a successful posttransplant anticancer immune response are the essential benefits of this treatment modality. The current donor-recipient matching criteria involve multiple factors but the only immunological barrier taken into consideration is the human leukocyte antigen system (HLA). However, an important factor affecting the success is the function of natural killer (NK) cells which are closely controlled by KIRs that interact with specific HLA class I ligands. KIR genes are encoded within 100¨C200£¿kb region of the leukocyte receptor complex (LRC) located on chromosome 19 (19q13.4) and segregated independently from the HLA genes. Most of HLA identical donor-recipient matched pairs are actually KIR mismatched. Innate system involves natural killer cells which through binding to their ligands can inhibit or activate the anticancer or antidonor reactivity arising from HLA recognition. The KIR genes belong to the most polymorphic structures between all surface receptors, second only to MHC, and are the key regulators of NK cells. Since these receptors are located on natural killer cells, they are called killer immunoglobulin-like receptors (KIRs). KIRs may exert inhibitory or activating functions through iKIR and aKIRs. There are nine iKIR and six aKIR
%U http://www.hindawi.com/journals/bmr/2012/271695/