Natural killer cell HLA-C epitopes and killer cell immunoglobulin-like receptors both influence outcome of mismatched unrelated donor bone marrow transplants.

Matching of donor and recipient for the class I human leukocyte antigen-C (HLA-C)-encoded natural killer (NK) epitopes has been reported to influence stem-cell (SC) graft outcome, but a consistent picture has not yet emerged. We have analyzed transplant outcome in 104 unrelated SC grafts in relation to NK epitope (C1 and C2) matching and donor killer cell immunoglobulin-like receptor (KIR) genotype. NK epitope mismatching in the rejection direction was strongly associated with an increased probability of rejection subsequent to engraftment. The prevalence of grades III-IV acute graft-vs-host disease (GVHD) was significantly higher and occurred significantly earlier when there was NK epitope mismatching in the GVH direction. Higher transplant-related mortality and lower disease-free survival rates were associated with epitope mismatching regardless of the mismatch direction. A greater number of KIR receptors, both activating and inhibitory, in the donor protected against grades III-IV GVHD and improved survival.

[1]  G. Ehninger,et al.  Role of KIR ligand incompatibility in hematopoietic stem cell transplantation using unrelated donors. , 2004, Blood.

[2]  F. Christiansen,et al.  The beneficial role of inhibitory KIR genes of HLA class I NK epitopes in haploidentically mismatched stem cell allografts may be masked by residual donor-alloreactive T cells causing GVHD. , 2004, Tissue antigens.

[3]  C. Craddock,et al.  The impact of donor KIR and patient HLA-C genotypes on outcome following HLA-identical sibling hematopoietic stem cell transplantation for myeloid leukemia. , 2004, Blood.

[4]  R. Handgretinger,et al.  Determinants of Antileukemia Effects of Allogeneic NK Cells 1 , 2004, The Journal of Immunology.

[5]  R. Handgretinger,et al.  T‐cell alloreactivity dominates natural killer cell alloreactivity in minimally T‐cell‐depleted HLA‐non‐identical paediatric bone marrow transplantation , 2003, British journal of haematology.

[6]  Franco Locatelli,et al.  Survival advantage with KIR ligand incompatibility in hematopoietic stem cell transplantation from unrelated donors. , 2003, Blood.

[7]  A. Poggi,et al.  Soluble HLA class I induces NK cell apoptosis upon the engagement of killer-activating HLA class I receptors through FasL-Fas interaction. , 2002, Blood.

[8]  Daniel J Weisdorf,et al.  Evaluation of KIR ligand incompatibility in mismatched unrelated donor hematopoietic transplants. Killer immunoglobulin-like receptor. , 2002, Blood.

[9]  Eric Mickelson,et al.  Killer Ig-Like Receptor Haplotype Analysis by Gene Content: Evidence for Genomic Diversity with a Minimum of Six Basic Framework Haplotypes, Each with Multiple Subsets1 , 2002, The Journal of Immunology.

[10]  D Middleton,et al.  A common KIR2DS4 deletion variant in the human that predicts a soluble KIR molecule analogous to the KIR1D molecule observed in the rhesus monkey. , 2002, Tissue antigens.

[11]  N. Schleinitz,et al.  Relevance of KIR gene polymorphisms in bone marrow transplantation outcome. , 2002, Human immunology.

[12]  Katia Perruccio,et al.  Effectiveness of Donor Natural Killer Cell Alloreactivity in Mismatched Hematopoietic Transplants , 2002, Science.

[13]  O. Mandelboim,et al.  Recognition of HLA-Cw4 but Not HLA-Cw6 by the NK Cell Receptor Killer Cell Ig-Like Receptor Two-Domain Short Tail Number 41 , 2001, The Journal of Immunology.

[14]  C. Witt,et al.  Population frequencies and putative haplotypes of the killer cell immunoglobulin-like receptor sequences and evidence for recombination. , 1999, Transplantation.

[15]  J. Strominger,et al.  Differential binding to HLA-C of p50-activating and p58-inhibitory natural killer cell receptors. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[16]  D. Hafler,et al.  Natural killer activating receptors trigger interferon gamma secretion from T cells and natural killer cells. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[17]  P Parham,et al.  Human diversity in killer cell inhibitory receptor genes. , 1997, Immunity.

[18]  Eric O Long,et al.  A new human gene complex encoding the killer cell inhibitory receptors and related monocyte/macrophage receptors , 1997, Current Biology.

[19]  K. Kärre.  How to recongnize a foreign submarine , 1997 .

[20]  M. Colonna,et al.  A human killer inhibitory receptor specific for HLA-A1,2. , 1996, Journal of immunology.

[21]  A. Nagler,et al.  The putative role of HLA-C recognition in graft versus host disease (GVHD) and graft rejection after unrelated bone marrow transplantation (BMT). , 1995, Experimental hematology.

[22]  Eric O Long,et al.  Killer cell inhibitory receptors specific for HLA-C and HLA-B identified by direct binding and by functional transfer. , 1995, Immunity.

[23]  C. Frégeau,et al.  DNA typing for bone marrow engraftment follow-up after allogeneic transplant: a comparative study of current technologies. , 1995, Bone marrow transplantation.

[24]  E D Thomas,et al.  1994 Consensus Conference on Acute GVHD Grading. , 1995, Bone marrow transplantation.

[25]  M. Colonna,et al.  Cloning of immunoglobulin-superfamily members associated with HLA-C and HLA-B recognition by human natural killer cells. , 1995, Science.

[26]  E. Brooks,et al.  Generation of allospecific natural killer cells by stimulation across a polymorphism of HLA-C. , 1993, Science.

[27]  J. Strominger,et al.  Alloantigen recognition by two human natural killer cell clones is associated with HLA-C or a closely linked gene. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[28]  M. Bennett,et al.  Murine natural killer cells and marrow graft rejection. , 1992, Annual review of immunology.

[29]  E. Ciccone,et al.  Identification of four subsets of human CD3-CD16+ natural killer (NK) cells by the expression of clonally distributed functional surface molecules: correlation between subset assignment of NK clones and ability to mediate specific alloantigen recognition , 1990, The Journal of experimental medicine.

[30]  H. Ljunggren,et al.  In search of the 'missing self': MHC molecules and NK cell recognition. , 1990, Immunology today.

[31]  Eric O Long,et al.  Specific lysis of allogeneic cells after activation of CD3- lymphocytes in mixed lymphocyte culture , 1988, The Journal of experimental medicine.