Human monoclonal HLA antibodies reveal interspecies crossreactive swine MHC class I epitopes relevant for xenotransplantation

Mulder, Arend; Kardol, M. J.; Arn, J S; Eijsink, Chantal; Franke, Marry E.I.; Schreuder, G. M. T.; Haasnoot, Geert W.; Doxiadis, Ilias I.N.; Sachs, David H.; Smith, Douglas M.; Claas, Frans H.J.

doi:10.1016/j.molimm.2009.10.004

Cited by 88 publications

(77 citation statements)

References 21 publications

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“…Fetal Hofbauer cells were gated out with CD45-PE-Cy5 (clone HI30) (BioLegend). Fusion protein binding was blocked by prior incubation with the mAb HP-3E4 (for KIR2DL1 and S1), a control isotype clone G155-228 (both Becton Dickinson) or the mAb WK4C11, generated from a hybridoma of B cells isolated from peripheral blood of multiparous women (21). WK4C11 reactivity was characterized against 96 common classical HLA-I allotypes using LABScreen Single Antigen beads (One Lambda) as previously described (7).…”

Section: Methodsmentioning

confidence: 99%

“…We next ascertained whether HLA-C on the surface of the extra-embryonic EVT is strictly maternal or paternal in origin, since many genes are imprinted in the placenta, or is co-dominantly expressed, as on all somatic cells. To do this we characterized the mAb WK4C11 (21) and found that it bound all C1 (apart from Cw7), but not C2, allotypes on normal cells including EVTs (Supplemental Table 1 and Supplemental Figure 1, A and B; supplemental material available online with this article; doi:10.1172/JCI43998DS1). Consistent with this reactivity, WK4C11 blocked binding of KIR2DL3-Fc proteins to a C1 transfectant, but not of 2DL1-Fc to a C2 transfectant (Supplemental Figure 1C).…”

Section: Hla-c Is Selectively Expressed By Evt At the Site Of Placentmentioning

confidence: 99%

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Maternal activating KIRs protect against human reproductive failure mediated by fetal HLA-C2

Hiby

Apps²,

Sharkey³

et al. 2010

J. Clin. Invest.

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Many common disorders of pregnancy are attributed to insufficient invasion of the uterine lining by trophoblast, fetal cells that are the major cell type of the placenta. Interactions between fetal trophoblast and maternal uterine NK (uNK) cells -specifically interactions between HLA-C molecules expressed by the fetal trophoblast cells and killer Ig-like receptors (KIRs) on the maternal uNK cells -influence placentation in human pregnancy. Consistent with this, pregnancies are at increased risk of preeclampsia in mothers homozygous for KIR haplotype A (KIR AA). In this study, we have demonstrated that trophoblast expresses both paternally and maternally inherited HLA-C surface proteins and that maternal KIR AA frequencies are increased in affected pregnancies only when the fetus has more group 2 HLA-C genes (C2) than the mother. These data raise the possibility that there is a deleterious allogeneic effect stemming from paternal C2. We found that this effect also occurred in other pregnancy disorders (fetal growth restriction and recurrent miscarriage), indicating a role early in gestation for these receptor/ligand pairs in the pathogenesis of reproductive failure. Notably, pregnancy disorders were less frequent in mothers that possessed the telomeric end of the KIR B haplotype, which contains activating KIR2DS1. In addition, uNK cells expressed KIR2DS1, which bound specifically to C2 + trophoblast cells. These findings highlight the complexity and central importance of specific combinations of activating KIR and HLA-C in maternal-fetal immune interactions that determine reproductive success. IntroductionThe main tissue location where maternal allo-recognition of the fetus occurs is in the uterus at the site of placentation, where fetal extravillous trophoblast cells (EVTs) invade and intermingle with maternal leukocytes (1). Uterine NK (uNK) cells account for approximately 70% of decidual leukocytes and are likely to be involved in placentation and thus fetal growth and development. We proposed that placentation is regulated as a result of interactions between maternal killer immunoglobulin-like receptors (KIRs) expressed by uNK cells and their cognate ligands, HLA-C molecules, displayed by invading fetal trophoblast cells (2, 3). The importance of NK cell KIR/HLA-C interactions in mediating allorecognition in the artificial context of BM transplantation (BMT) is well known (4). The only physiological situation in which NK allo-recognition occurs is during pregnancy.The function of EVT is to access the maternal blood supply during placentation, when trophoblast invades the walls of the spiral arteries, converting them to high-conductance vessels (1).

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Section: Methodsmentioning

confidence: 99%

Section: Hla-c Is Selectively Expressed By Evt At the Site Of Placentmentioning

confidence: 99%

Maternal activating KIRs protect against human reproductive failure mediated by fetal HLA-C2

Hiby

Apps²,

Sharkey³

et al. 2010

J. Clin. Invest.

Self Cite

443

335

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“…36 Importantly, the isolated T-cell clones were child derived as they stained with HLA-specific mAbs (kindly provided by A. Mulder, Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands) specific for the HLA allele the UCB sample did not share with her mother. 37,38 We used the HY responses as proof of principle. Both HLA-A2-and HLA-B7-restricted HY-specific CTLs were isolated.…”

Section: Discussionmentioning

confidence: 99%

Transmaternal cell flow leads to antigen-experienced cord blood

Dierselhuis

Blokland

Pool

et al. 2012

Blood

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“…Cells were analyzed for HLA epitope expression before and after expansion with custom-made, in-house human HLA epitope specific monoclonal antibodies [47][48][49][50].…”

Section: Cd34mentioning

confidence: 99%

Thrombopoietin Treatment of One Graft in a Double Cord Blood Transplant Provides Early Platelet Recovery While Contributing to Long-Term Engraftment in NSG Mice

Brand

et al. 2015

Stem Cells and Development

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Human cord blood (CB) hematopoietic stem cell (HSC) transplants demonstrate delayed early neutrophil and platelet recovery and delayed longer term immune reconstitution compared to bone marrow and mobilized peripheral blood transplants. Despite advances in enhancing early neutrophil engraftment, platelet recovery after CB transplantation is not significantly altered when compared to contemporaneous controls. Recent studies have identified a platelet-biased murine HSC subset, maintained by thrombopoietin (TPO), which has enhanced capacity for short-and long-term platelet reconstitution, can self-renew, and can give rise to myeloid-and lymphoidbiased HSCs. In previous studies, we have shown that transplantation of human CB CD34+ cells precultured in TPO as a single graft accelerates early platelet recovery as well as yielding long-term repopulation in immunedeficient mice. In this study, using a double CB murine transplant model, we investigated whether TPO cultured human CB CD34+ cells have a competitive advantage or disadvantage over untreated human CB CD34 + cells in terms of (1) short-term and longer term platelet recovery and (2) longer term hematological recovery. Our studies demonstrate that the TPO treated graft shows accelerated early platelet recovery without impairing the platelet engraftment of untreated CD34 + cells. Notably, this was followed by a dominant contribution to platelet production through the untreated CD34 + cell graft over the intermediate to longer term. Furthermore, although the contribution of the TPO treated graft to long-term hematological engraftment was reduced, the TPO treated and untreated grafts both contributed significantly to long-term chimerism in vivo.

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Human monoclonal HLA antibodies reveal interspecies crossreactive swine MHC class I epitopes relevant for xenotransplantation

Cited by 88 publications

References 21 publications

Maternal activating KIRs protect against human reproductive failure mediated by fetal HLA-C2

Maternal activating KIRs protect against human reproductive failure mediated by fetal HLA-C2

Transmaternal cell flow leads to antigen-experienced cord blood

Thrombopoietin Treatment of One Graft in a Double Cord Blood Transplant Provides Early Platelet Recovery While Contributing to Long-Term Engraftment in NSG Mice

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