scholarly journals Back signaling of HLA class I molecules and T/ NK cell receptor ligands in epithelial cells reflects the rejection‐specific microenvironment in renal allograft biopsies

2019 ◽  
Vol 19 (10) ◽  
pp. 2692-2704 ◽  
Author(s):  
Johanna Egelkamp ◽  
Evgeny Chichelnitskiy ◽  
Jenny F. Kühne ◽  
Franziska Wandrer ◽  
Kerstin Daemen ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Renal Allograft ◽  
Nk Cell ◽  
Hla Class I ◽  
Cell Receptor ◽  
Class I ◽  
Receptor Ligands ◽  
Hla Class I Molecules ◽  
Nk Cell Receptor

Identification of Natural Killer Cell Receptor Phenotypes Associated with Leukemia.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2997-2997
Author(s):  
Sonja J. Verheyden ◽  
Michel Bernier ◽  
Christian J. Demanet
Keyword(s):  
Nk Cells ◽  
Natural Killer ◽  
Nk Cell ◽  
Killer Cell ◽  
Hla Class I ◽  
Cell Receptor ◽  
Innate Immune ◽  
Class I ◽  
Leukemic Cells ◽  
Hla Class I Molecules

Abstract Introduction: Natural Killer (NK) cells play a key role in defense against tumor cells that have the capacity to downregulate Human Leukocyte Antigen (HLA) class I expression. It has been reported that leukemic cells can have down-regulated expression of HLA class I molecules. Apparently, the NK cells of these patients are not able to destroy these leukemic cells and may allow malignant cells to escape from innate immune control. This failure may be due to the fact that NK cells are part of the malignant clone and therefore might have a decreased function. An alternative hypothesis could be that these patients may display a NK cell Receptor (NKR) genotype incapable of destroying leukemic cells with aberrant expression of HLA class I molecules. The polymorphic nature of the NKR genes generates diverse repertoires in the human population, which display specificity in the innate immune response. Materials and Methods: In the present study, 11 Killer cell Immunoglobulin-like Receptor (KIRs) and 2 CD94/NKG2 receptors were genotyped by PCR-SSP in 96 leukemic patients and 148 healthy Caucasians. Results and Conclusion: We report a significant increased frequency of the more inhibitory AB KIR phenotype in leukemic patients compared to the controls (31.1% in healthy controls vs. 51.0% in leukemic patients, Pc = 0.002), which is related to the high prevalence of the inhibitory KIR2DL2 in this population (Pc = 0.007). Moreover, two specific KIR phenotypes AB1 and AB9, including all inhibitory KIRs, were significantly associated with leukemic patients. Our study suggests that an important percentage of leukemic patients express a KIR phenotype in favor of escape from NK cell immunity.

scholarly journals Activating NK cell receptor ligands are differentially expressed during progression to cervical cancer

2008 ◽  
Vol 123 (10) ◽  
pp. 2343-2353 ◽  
Author(s):  
Sonja Textor ◽  
Matthias Dürst ◽  
Lars Jansen ◽  
Rosita Accardi ◽  
Massimo Tommasino ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Nk Cell ◽  
Cell Receptor ◽  
Differentially Expressed ◽  
Receptor Ligands ◽  
Nk Cell Receptor

Amnion Epithelial Cells, in Contrast to Trophoblast Cells, Express All Classical HLA Class I Molecules Together With HLA-G

1997 ◽  
Vol 37 (2) ◽  
pp. 161-171 ◽  
Author(s):  
Astrid Hammer ◽  
Heinz Hutter ◽  
Astrid Blaschitz ◽  
Wolfgang Mahnert ◽  
Michaele Hartmann ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Hla Class I ◽  
Class I ◽  
Trophoblast Cells ◽  
Hla Class I Molecules ◽  
Amnion Epithelial Cells

scholarly journals Human CD8 transgene regulation of HLA recognition by murine T cells.

1995 ◽  
Vol 182 (5) ◽  
pp. 1315-1325 ◽  
Author(s):  
D M LaFace ◽  
M Vestberg ◽  
Y Yang ◽  
R Srivastava ◽  
J DiSanto ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Hla Class I ◽  
Cell Receptor ◽  
Class I ◽  
Antigenic Peptides ◽  
Cell Repertoire ◽  
Repertoire Selection ◽  
Hla Class I Molecules ◽  
Cell Expression

A series of human CD8 transgenic (hCD8 Tg) mice with differential expression in the thymus and periphery were produced to investigate CD8 coreceptor regulation of repertoire selection and T cell responses. Expression of hCD8 markedly enhanced responses to both HLA class I molecules and hybrid A2/Kb molecules providing functional evidence for a second interaction site, outside of the alpha 3 domain, which is essential for optimal coreceptor function. Peripheral T cell expression of hCD8 was sufficient to augment responsiveness to HLA class I, as hCD8 Tg mice which lacked thymic expression responded as well as mice expressing hCD8 in the thymus and periphery. Both murine CD8+ and CD4+ T cells expressing hCD8 transgenes exhibited markedly enhanced responses to foreign HLA class I, revealing the ability of T cell receptor repertoires selected on either murine class I or class II to recognize human class I major histocompatibility complex (MHC). In contrast to recognition of foreign class I, thymic expression of hCD8 transgenes was absolutely required to enhance recognition of antigenic peptide restricted by self-HLA class I. Thus, our studies revealed disparate requirements for CD8 coreceptor expression in the thymus for selection of a T cell repertoire responsive to foreign MHC and to antigenic peptides bound to self-MHC, providing a novel demonstration of positive selection that is dependent on human CD8.

Analyses of HLA-C–specific KIR repertoires in donors with group A and B haplotypes suggest a ligand-instructed model of NK cell receptor acquisition

Blood ◽  
2011 ◽  
Vol 117 (1) ◽  
pp. 98-107 ◽  
Author(s):  
Kathrin Schönberg ◽  
Martina Sribar ◽  
Jürgen Enczmann ◽  
Johannes C. Fischer ◽  
Markus Uhrberg
Keyword(s):  
Nk Cells ◽  
Nk Cell ◽  
Hla Class I ◽  
Cell Receptor ◽  
Suppressive Effect ◽  
Class I ◽  
Nk Cell Differentiation ◽  
Group A ◽  
Common Group ◽  
Group B

Abstract To determine the influence of KIR and HLA class I polymorphism on human NK cell repertoires, 32 different clonotypes representing all possible combinations of 4 inhibitory KIR and NKG2A were analyzed by multicolor flow cytometry. In donors homozygous for the common group A KIR haplotype, a significant influence of HLA-C ligands was seen: KIR repertoires were dominated by clonotypes expressing a single KIR for the respective cognate ligand, either the C1-specific KIR2DL3 or C2-specific KIR2DL1. In contrast, in donors possessing the polymorphic group B haplotypes, a similar adaptation to cognate HLA-C was lacking. We suggest that this discrepancy is largely the result of a suppressive effect of the group B–specific KIR2DL2 on the frequency of KIR2DL1+ NK cells. In functional assays, KIR2DL2 not only recognized C1 but also C2 ligands, showing overlapping specificity with KIR2DL1. Moreover, using an NK cell differentiation assay we show sequential acquisition of KIR2DL2 before KIR2DL1 on developing NK cells. Together, these observations are compatible with a ligand-instructed model of NK cell education, in which recognition of HLA class I by an inhibitory receptor (KIR2DL2) suppresses subsequent expression of a second receptor (KIR2DL1) of related specificity. Importantly, the ligand-instructed model fits to the observed KIR repertoires in both broad KIR haplotype groups.

scholarly journals The Emerging Role of HLA-E-Restricted CD8+T Lymphocytes in the Adaptive Immune Response to Pathogens and Tumors

2010 ◽  
Vol 2010 ◽  
pp. 1-8 ◽  
Author(s):  
Gabriella Pietra ◽  
Chiara Romagnani ◽  
Claudia Manzini ◽  
Lorenzo Moretta ◽  
Maria Cristina Mingari
Keyword(s):  
Cell Function ◽  
Nk Cell ◽  
Adaptive Immune Response ◽  
Human Leukocyte ◽  
Hla Class I ◽  
Cell Receptor ◽  
Class I ◽  
Mhc Class I Molecule ◽  
Associated Proteins ◽  
Acquired Immune Responses

Human leukocyte antigen (HLA)-E is a nonclassical major histocompatibility complex (MHC) class I molecule of limited sequence variability that is expressed by most tissues albeit at low levels. HLA-E has been first described as the ligand of CD94/NKG2 receptors expressed mainly by natural killer (NK) cells, thus confining its role to the regulation of NK-cell function. However, recent evidences obtained by our and other groups indicate that HLA-E complexed with peptides can interact withαβT-cell receptor (TCR) expressed on CD8+T cells. Although, HLA-E displays a selective preference for nonameric peptides, derived from the leader sequence of various HLA class I alleles, several reports indicate that it can present also “noncanonical” peptides derived from both stress-related and pathogen-associated proteins. Because HLA-E displays binding specificity for innate CD94/NKG2 receptors, as well as all the features of an antigen-presenting molecule, its role in both natural and acquired immune responses has recently been re-evaluated.

Analysis of natural killer cells in TAP2-deficient patients: expression of functional triggering receptors and evidence for the existence of inhibitory receptor(s) that prevent lysis of normal autologous cells

Blood ◽  
2002 ◽  
Vol 99 (5) ◽  
pp. 1723-1729 ◽  
Author(s):  
Massimo Vitale ◽  
Jacques Zimmer ◽  
Roberta Castriconi ◽  
Daniel Hanau ◽  
Lionel Donato ◽  
...  
Keyword(s):  
Nk Cells ◽  
Natural Killer ◽  
Antigen Processing ◽  
Nk Cell ◽  
Hla Class I ◽  
Surface Expression ◽  
Class I ◽  
Inhibitory Receptor ◽  
Surface Receptors ◽  
Hla Class I Molecules

Natural killer (NK) cells are characterized by the ability to kill cells that lack HLA class I molecules while sparing autologous normal (HLA class I+) cells. However, patients with transporter-associated antigen processing (TAP) deficiency, though displaying strong reductions of HLA class I surface expression, in most instances do not experience NK-mediated autoimmune phenomena. A possible mechanism by which TAP−/− NK cells avoid autoreactivity against autologous HLA class I–deficient cells could be based on either quantitative or qualitative defects of surface receptors involved in NK cell triggering. In this study we show that NK cells derived from 2 patients with TAP2−/− express normal levels of all known triggering receptors. As revealed by the analysis of polyclonal and clonal NK cells, these receptors display normal functional capabilities and allow the killing of a panel of NK-susceptible targets, including autologous B-LCLs. On the other hand, TAP2−/− NK cells were unable to kill either allogeneic (HLA class I+) or autologous (HLA class I− ) phytohemagglutinin (PHA) blasts even in the presence of anti-HLA class I monoclonal antibody. These data suggest that TAP2−/− NK cells express still unknown inhibitory receptor(s) capable of down-regulating the NK cell cytotoxicity on binding to surface ligand(s) expressed by T cell blasts. Functional analyses, both at the polyclonal and at the clonal level, are consistent with the concept that the putative inhibitory receptor is expressed by virtually all TAP2−/− NK cells, whereas it is present only in rare NK cells from healthy persons. Another possibility would be that TAP2−/− NK cells are missing a still unidentified triggering receptor involved in NK cell-mediated killing of PHA blasts.

Sign in / Sign up

Export Citation Format

Share Document