scholarly journals Crystal Structure of the Human Natural Killer Cell Activating Receptor KIR2DS2 (CD158j)

2003 ◽  
Vol 197 (7) ◽  
pp. 933-938 ◽  
Author(s):  
Xavier Saulquin ◽  
Louis N. Gastinel ◽  
Eric Vivier

Killer cell Ig-like receptors (KIRs) regulate the function of human natural killer and T cell subsets. A feature of the KIR locus is the clustering of homologous genes encoding for inhibitory and activating KIR. Inhibitory and activating KIR differ for ligand specificities and/or affinities. In particular, we show here with KIR tetramers that activating KIR2DS2 does not bind HLA-Cw3 molecules recognized by inhibitory KIR2DL2, despite 99% extracellular amino acid identity. We also report the 2.3-Å structure of KIR2DS2, which reveals subtle displacements of two residues (Tyr45 and Gln71) involved in the interaction of KIR2DL2 with HLA-Cw3. These results show that KIR molecules cannot tolerate any variability in their three-dimensional structure without altering their MHC class I recognition capacities. Therefore, the mode of recognition used by KIR largely differs from the conformational changes that characterize T cell receptor or NKG2D interaction with their respective ligands.

2000 ◽  
Vol 124 (10) ◽  
pp. 1510-1513 ◽  
Author(s):  
Paulette Mhawech ◽  
L. Jeffrey Medeiros ◽  
Carlos Bueso-Ramos ◽  
Donna M. Coffey ◽  
Alfredo F. Gei ◽  
...  

Abstract Non-Hodgkin lymphomas (NHL) can involve the gynecologic tract, most often as a manifestation of systemic involvement, and most cases reported have been of B-cell lineage. We describe 2 women with natural killer (NK)-cell lymphoma involving the gynecologic tract that initially presented with vaginal bleeding. In case 1, the patient had a stage IE nasal-type NK-cell lymphoma involving the cervix. The tumor was composed of medium-sized, irregular lymphoid cells with angioinvasion and necrosis. In case 2, the patient had a stage IV blastoid NK-cell lymphoma/leukemia infiltrating all organs in a hysterectomy and bilateral salpingo-oophorectomy specimen. Subsequent biopsy specimens revealed that the bone marrow and lymph nodes were also involved. The neoplasm was composed of small to medium lymphoid cells with fine nuclear chromatin. Case 1 was assessed immunohistochemically and the neoplastic cells were positive for CD3, CD56, and TIA-1. Case 2 was analyzed using both immunohistochemical and flow cytometry methods. The neoplastic cells were positive for cytoplasmic CD3, CD4, CD7, CD43, CD45, and CD56 and were negative for surface CD3. Both cases were negative for Epstein-Barr virus (EBV) ribonucleic acid (RNA) and molecular studies showed no evidence of T-cell receptor γ chain gene rearrangements. The immunophenotype and absence of T-cell receptor gene rearrangements support NK-cell origin. We report these cases to illustrate that NK-cell lymphomas can involve, and rarely arise in, the gynecologic tract.


1997 ◽  
Vol 84 (3_suppl) ◽  
pp. 1296-1298 ◽  
Author(s):  
Tsutomu Kamei ◽  
Hiroaki Kumano ◽  
Sumio Masumura

For 8 medical students influences of psychological stress or humor on T-cell subset percentages and natural killer cell activity were investigated by measuring these parameters before and after an examination and before and after watching a comedy video. Although T-cell subsets were not significantly affected by either stimulus and natural killer cell activity was not affected by the examination, the latter was significantly decreased after watching the comedy video.


2008 ◽  
Vol 22 (S1) ◽  
Author(s):  
Stephen O Mathew ◽  
Krithi K Rao ◽  
Nowland D Bambard ◽  
Porunelloor A Mathew

Author(s):  
Elena Vendrame ◽  
Julia L. McKechnie ◽  
Thanmayi Ranganath ◽  
Nancy Q. Zhao ◽  
Arjun Rustagi ◽  
...  

Blood ◽  
1994 ◽  
Vol 84 (8) ◽  
pp. 2721-2725 ◽  
Author(s):  
A Tefferi ◽  
CY Li ◽  
TE Witzig ◽  
MV Dhodapkar ◽  
SH Okuno ◽  
...  

Abstract We review the clinical manifestations and long-term outlook of patients with chronic natural killer (NK) cell lymphocytosis. After reviewing more than 1,500 peripheral blood lymphoid flow cytometry reports and molecular genetics data from patients with suspected large granular lymphocyte (LGL) proliferation, we identified 10 patients (median age at diagnosis, 60 years; range, 35 to 76 years; male:female ratio, 3:2) with persistent (greater than 6 months) increase in phenotypically determined NK cells (CD3-CD16+). Southern blot analysis performed on 9 patients showed no clonal T-cell receptor gene rearrangements. Disease duration was measured from time of initial recognition of LGL or NK cell excess (greater than 40% of the lymphocyte fraction). Clinical data from these 10 patients were compared with those from 68 patients with T-cell LGL (T-LGL) leukemia. Currently, all patients are alive (median disease duration, 5 years; range, 0.8 to 8 years). Associated disease manifestations included pure red blood cell aplasia, recurrent neutropenia, recurrent neutropenic sepsis, and vasculitic syndromes, all of which were responsive to immunosuppressive therapy. No patient had palpable lymphadenopathy or splenomegaly. Compared with the patients with T-LGL leukemia, patients with chronic NK cell leukemia has similar lymphocyte counts, associated conditions, treatment responses, and survival but had less neutropenia and anemia.


2011 ◽  
Vol 286 (18) ◽  
pp. 15973-15979 ◽  
Author(s):  
Bianca L. Bozna ◽  
Paolo Polzella ◽  
Christian Rankl ◽  
Rong Zhu ◽  
Mariolina Salio ◽  
...  

Invariant natural killer T (iNKT) cells are a population of T lymphocytes that play an important role in regulating immunity to infection and tumors by recognizing endogenous and exogenous CD1d-bound lipid molecules. Using soluble iNKT T cell receptor (TCR) molecules, we applied single molecule force spectroscopy for the investigation of the iNKT TCR affinity for human CD1d molecules loaded with glycolipids differing in the length of the phytosphingosine chain using either recombinant CD1d molecules or lipid-pulsed THP1 cells. In both settings, the dissociation of the iNKT TCR from human CD1d molecules loaded with the lipid containing the longer phytosphingosine chain required higher unbinding forces compared with the shorter phytosphingosine lipid. Our findings are discussed in the context of previous results obtained by surface plasmon resonance measurements. We present new insights into the energy landscape and the kinetic rate constants of the iNKT TCR/human CD1d-glycosphingolipid interaction and emphasize the unique potential of single molecule force spectroscopy on living cells.


2017 ◽  
Vol 292 (27) ◽  
pp. 11413-11422 ◽  
Author(s):  
Felix A. Deuss ◽  
Benjamin S. Gully ◽  
Jamie Rossjohn ◽  
Richard Berry

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