HLA class I specificity for natural killer cell receptor CD94/NKG2A: Two for one in more ways than one

Yokoyama, Wayne M.

doi:10.1073/pnas.95.9.4791

Cited by 19 publications

(11 citation statements)

References 44 publications

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“…Inhibition of lysis was mediated by the CD94/NKG2A heterodimer, by recognition of HLA-E, which is expressed by all the cells of an individual that express normal amount of classic MHC class I molecules. 23,38 High expression of CD94/NKG2A by immature NK cells in murine models appears to prevent most neonatal and prenatal NK cells from attacking self-cells. 39,40 As we have seen here, myeloid leukemic blasts also express HLA-E, and this expression inhibited their lysis by NK cells isolated ex vivo after haplo-SCT.…”

Section: Discussionmentioning

confidence: 99%

NK-cell reconstitution after haploidentical hematopoietic stem-cell transplantations: immaturity of NK cells and inhibitory effect of NKG2A override GvL effect

Nguyen

Dhédin

Vernant

et al. 2005

Blood

229

204

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Natural killer (NK) cell alloreactivity is reported to mediate strong GvL (graft versus leukemia) effect in patients after haploidentical stem-cell transplantation (SCT) for acute myeloid leukemia (AML). Because subsequent immune reconstitution remains a major concern, we studied NK-cell recovery in 10 patients with AML who received haplomismatched SC transplants, among whom no GvL effect was observed, despite the mismatched immunoglobulin-like receptor (KIR) ligand in the GvH direction for 8 of 10 patients. NK cells generated after SCT exhibited an immature phenotype: the cytotoxic CD3 ؊ CD56 dim subset was small, expression of KIRs and NKp30 was reduced, while CD94/NKG2A expression was increased. This phenotype was associated to in vitro lower levels of cytotoxicity against a K562 cell line and against primary mismatched AML blasts than donor samples. This impaired lysis was correlated with CD94/NKG2A expression in NK cells. Blockading CD94/NKG2A restored lysis against the AML blasts, which all expressed HLA-E, the ligand for CD94/ NKG2A. Our present study allows a better understanding of the NK-cell differentiation after SCT. These results revealed that the NK cells generated after haplomismatched SCT are blocked at an immature state characterized by specific phenotypic features and impaired functioning, having potential impact for immune responsiveness and transplantation outcome. (Blood. 2005;105:4135-4142)

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Section: Discussionmentioning

confidence: 99%

NK-cell reconstitution after haploidentical hematopoietic stem-cell transplantations: immaturity of NK cells and inhibitory effect of NKG2A override GvL effect

Nguyen

Dhédin

Vernant

et al. 2005

Blood

229

204

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“…The target K562 cells lack expression of classical MHC class I antigens; however, the expression of nonclassical MHC antigens on their surface has not been ruled out. The nonclassical MHC class I antigens are also known to bind some NK receptor [Yokoyama, 1998]. …”

Section: Determination Of Nk Activitymentioning

confidence: 99%

“…The NKG2/CD94 family receptors are generally expressed as heterodimers with an invariant type II integral membrane protein, CD94 and are encoded by four distinct NKG2A, C, D, and E genes. Similar to KIR, these receptors may be inhibitory (A) or activatory (C and D), and recognize nonclassical MHC proteins, e.g., HLA-E, MICA and MICB as ligands on target cells [Braud et al, 1998;Lanier, 1998a,b;Leibson, 1998;Yokoyama, 1998;Long, 1999].…”

Section: Introductionmentioning

confidence: 99%

Modulation of expression of the MHC class I‐binding natural killer cell receptors, and NK activity in relation to viral load in HIV‐infected/AIDS patients

Ahmad

Sindhu

Tran

et al. 2001

Journal of Medical Virology

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The natural killer (NK) cells play an important role in viral infections via their spontaneous cytolytic activity against virus-infected cells as well as via secreting a variety of soluble mediators. The MHC class I-binding NK receptors of these cells have emerged as the most important regulators of the effector activities of cytolytic cells (both NK and CTL). We have studied the modulation of NK activity and the expression of NK receptors in HIV-infected/AIDS patients and report here that the NK activities of the patients with the lowest plasma HIV load were minimal and vice versa, suggesting a decrease in this activity following suppression of HIV replication. Interestingly, the NK activity correlated negatively with the peripheral blood CD4+ T-cell counts of these patients. Furthermore, these patients showed decreased percentages of CD56+ cells expressing NK receptors of the immunoglobulin superfamily, whereas the percentages of CD8+ cells expressing these receptors were increased. Moreover, the expression of C-type lectin-like NK receptor-associated invariant molecule CD94 was increased on CD8+ cells in these patients as compared with HIV-seronegative controls. These changes in the expression of NK receptors were also evident within groups of these patients having different viral loads. These results show, for the first time, decreased innate immunity and changes in the expression of NK receptors on cytolytic cells in relation to viral burden in HIV-infected/AIDS patient.

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“…In the context of implantation the important findings are that NK cells do express receptors capable of recognizing HLA class I molecules (Moretta & Moretta, 1997;Yokoyama, 1998). The first family of NK receptors to be found belong to the immunoglobulin superfamily, and are known as killer inhibitory receptors (KIR) because interaction with class I HLA molecules leads to the transmission of negative signals that will inhibit cytolysis or cytokine production.…”

Section: Trophoblast -Natural Killer Cell Interactionmentioning

confidence: 99%

“…The second NK cell receptor family for class I HLA molecules is known as CD94-NKG2 (Phillips et al Yokoyama, 1998). These receptors are encoded by NKassociated genes located closely together as an NK complex which encodes for type I1 membrane glycoproteins with an external lectin-like domain (NK lectins).…”

Section: Trophoblast -Natural Killer Cell Interactionmentioning

confidence: 99%

The influence of the maternal uterine immune response on placentation in human subjects

King

Loke

1999

Proc. Nutr. Soc.

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The immunological relationship beween the mammalian fetus and its mother during pregnancy has been considered similar to that between a transplanted allograft and its recipient ever since Medawar (1953) first proposed the concept of the ‘fetus as an allograft’ in the early 1950s. Based on this analogy, it has been assumed that implantation of the fetal placenta in the uterus would be controlled similarly by a maternal immune response mediated by T-cells recognizing paternally-derived alloantigens expressed by the placenta. Surprisingly, recent evidence suggests that implantation might involve predominantly a novel allogeneic recognition system based on natural killer cells rather than T-cells (Loke & King, 1995). The cellular and molecular basis of this local immune interaction between the fetal placenta and maternal uterus is now the focus of intense research interest. Since aberrant implantation can cause a variety of clinical problems, including miscarriage, intrauterine growth retardation and pre-eclampsia, an understanding of the immunological mechanism by which this process is controlled could lead to the development of regimens to improve fetal growth and development.

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HLA class I specificity for natural killer cell receptor CD94/NKG2A: Two for one in more ways than one

Cited by 19 publications

References 44 publications

NK-cell reconstitution after haploidentical hematopoietic stem-cell transplantations: immaturity of NK cells and inhibitory effect of NKG2A override GvL effect

NK-cell reconstitution after haploidentical hematopoietic stem-cell transplantations: immaturity of NK cells and inhibitory effect of NKG2A override GvL effect

Modulation of expression of the MHC class I‐binding natural killer cell receptors, and NK activity in relation to viral load in HIV‐infected/AIDS patients

The influence of the maternal uterine immune response on placentation in human subjects

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