scholarly journals Antibodies as antigens. The use of mouse monoclonal antibodies to focus human T cells against selected targets.

1988 ◽  
Vol 167 (2) ◽  
pp. 345-352 ◽  
Author(s):  
A Lanzavecchia ◽  
S Abrignani ◽  
D Scheidegger ◽  
R Obrist ◽  
B Dörken ◽  
...  
Keyword(s):  
T Cells ◽  
Monoclonal Antibodies ◽  
Cell Surface ◽  
Mhc Class Ii ◽  
Class Ii ◽  
Cell Surface Molecules ◽  
Tumor Patients ◽  
Surface Molecules ◽  
Human T Cells ◽  
Positive Target

We found that three tumor patients treated with mouse mAbs have T cells that recognize processed mouse Ig on autologous APC in a class II-restricted fashion, and we have shown that mouse mAbs directed against various cell surface molecules can be used as antigens to focus these T cells on an MHC class II-positive target of choice.

MHC Class II alpha/beta Heterodimeric Cell Surface Molecules Expressed from a Single Proviral Genome

1999 ◽  
Vol 10 (14) ◽  
pp. 2397-2405 ◽  
Author(s):  
Hideaki Shimada ◽  
Sharon Germana ◽  
Kai-Christian Sonntag ◽  
Papia Banerjee ◽  
Daniel Moore ◽  
...  
Keyword(s):  
Cell Surface ◽  
Mhc Class Ii ◽  
Class Ii ◽  
Cell Surface Molecules ◽  
Proviral Genome ◽  
Surface Molecules ◽  
Alpha Beta ◽  
Class Ii Alpha

Human T Cells with Distinct Specificities Mediate Graft-Versus-Leukemia Reactivity and Xenogeneic Graft-Versus-Host Disease in a NOD/Scid Mouse Model for Human Acute Leukemia.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1330-1330
Author(s):  
Sanja Stevanovic ◽  
Bart Nijmeijer ◽  
Marianke LJ Van Schie ◽  
Roelof Willemze ◽  
Marieke Griffioen ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Mhc Class I ◽  
Mhc Class Ii ◽  
Class Ii ◽  
Cd4 T Cell ◽  
Class I ◽  
T Cell Clones ◽  
Cell Clones ◽  
Human T Cells

Abstract Abstract 1330 Poster Board I-352 Immunodeficient mice inoculated with human leukemia can be used as a model to investigate Graft-versus-Leukemia (GvL) effects of donor lymphocyte infusions (DLIs). In addition to GvL reactivity, treatment with DLI induces xenogeneic Graft-versus-Host Disease (GvHD) in mice, characterized by pancytopenia and weight loss. In patients treated with DLI for relapsed or residual leukemia after allogeneic stem cell transplantation, immune responses against non-leukemic cells may also cause GvHD. It has been suggested that GvL reactivity and GvHD, which co-develop in vivo, can be separated and that distinct T cells exist with the specific capacity to mediate GvL reactivity or GvHD. Since adoptive T cell transfer models that allow analysis of separation of GvL and GvHD are rare, we aimed to establish whether GvL reactivity and xenogeneic GvHD could be separated using our model of human leukemia-engrafted NOD/scid mouse after treatment with human donor T cells. In this study, non-conditioned NOD/scid mice engrafted with primary human acute lymphoblastic leukemic cells were treated with CD3+ DLI. Established tumors were effectively eliminated by emerging human T cells, but also induced xenogeneic GvHD. Flowcytometric analysis demonstrated that the majority of emerging CD8+ and CD4+ T cells were activated (HLA-DR+) and expressed an effector memory phenotype (CD45RA-CD45RO+CCR7-). To investigate whether GvL reactivity and xenogeneic GvHD were mediated by the same T cells showing reactivity against both human leukemic and murine cells, or displaying distinct reactivity against human leukemic and murine cells, we clonally isolated and characterized the T cells during the GvL response and xenogeneic GvHD. T cell clones were analyzed for reactivity against primary human leukemic cells and primary NOD/scid hematopoietic (BM and spleen cells) and non-hematopoietic (skin fibroblasts) cells in IFN-g ELISA. Isolated CD8+ and CD4+ T cell clones were shown to recognize either human leukemic or murine cells, indicating that GvL response and xenogeneic GvHD were mediated by different human T cells. Flowcytometric analysis demonstrated that all BM and spleen cells expressed MHC class I, whereas only 1-3 % of the cells were MHC class II +. Primary skin fibroblasts displayed low MHC class I and completely lacked MHC class II expression. Xeno-reactive CD8+ T cell clones were shown to recognize all MHC class I + target cells and xeno-reactive CD4+ T cells clones displayed reactivity only against MHC class II + target cells. To determine the MHC restriction of xeno-reactive T cell clones, NOD/scid bone marrow (BM) derived dendritic cells (DC) expressing high levels of murine MHC class I and class II were tested for T cell recognition in the presence or absence of murine MHC class I and class II monoclonal antibodies in IFN-g ELISA. Xeno-reactive CD8+ T cell clones were shown to be MHC class I (H-2Kd or H-2Db) restricted, whereas xeno-reactive CD4+ T cell clones were MHC class II (I-Ag7) restricted, indicating that xeno-reactivity reflects genuine human T cell response directed against allo-antigens present on murine cells. Despite production of high levels of IFN-gamma, xeno-reactive CD8+ and CD4+ T cell clones failed to exert cytolytic activity against murine DC, as determined in a 51Cr-release cytotoxicity assay. Absence of cytolysis by CD8+ T cell clones, which are generally considered as potent effector cells, may be explained by low avidity interaction between human T cells and murine DC, since flowcytometric analysis revealed sub-optimal activation of T cells as measured by CD137 expression and T cell receptor downregulation upon co-culture with murine DC, and therefore these results indicate that xenogeneic GvHD in this model is likely to be mediated by cytokines. In conclusion, in leukemia-engrafted NOD/scid mice treated with CD3+ DLI, we show that GvL reactivity and xenogeneic GvHD are mediated by separate human T cells with distinct specificities. All xeno-reactive T cell clones showed genuine recognition of MHC class I or class II associated allo-antigens on murine cells similar as GvHD-inducing human T cells. These data suggest that our NOD/scid mouse model of human acute leukemia may be valuable for studying the effectiveness and specificity of selectively enriched or depleted T cells for adoptive immunotherapy. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Generation of Monoclonal Antibodies Specific for Cell Surface Molecules Expressed on Early Mouse Endoderm

Stem Cells ◽  
2009 ◽  
Vol 27 (9) ◽  
pp. 2103-2113 ◽  
Author(s):  
Paul Gadue ◽  
Valerie Gouon-Evans ◽  
Xin Cheng ◽  
Ewa Wandzioch ◽  
Kenneth S Zaret ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Cell Surface ◽  
Cell Surface Molecules ◽  
Surface Molecules ◽  
Early Mouse

scholarly journals Identification and Characterization of Two Novel Staphylococcal Enterotoxins, Types S and T

2008 ◽  
Vol 76 (11) ◽  
pp. 4999-5005 ◽  
Author(s):  
Hisaya K. Ono ◽  
Katsuhiko Omoe ◽  
Ken'ichi Imanishi ◽  
Yoshihiro Iwakabe ◽  
Dong-Liang Hu ◽  
...  
Keyword(s):  
T Cells ◽  
Mhc Class Ii ◽  
Food Poisoning ◽  
Cell Receptor ◽  
Class Ii ◽  
Intragastric Administration ◽  
Delayed Reaction ◽  
Staphylococcal Enterotoxins ◽  
Human T Cells ◽  
Antigen Presenting

ABSTRACT In addition to two known staphylococcal enterotoxin-like genes (selj and selr), two novel genes coding for two superantigens, staphylococcal enterotoxins S and T (SES and SET), were identified in plasmid pF5, which is harbored by food poisoning-related Staphylococcus aureus strain Fukuoka 5. This strain was implicated in a food poisoning incident in Fukuoka City, Japan, in 1997. Recombinant SES (rSES) specifically stimulated human T cells in a T-cell receptor Vβ9- and Vβ16-specific manner in the presence of major histocompatibility complex (MHC) class II+ antigen-presenting cells (APC). rSET also stimulated T cells in the presence of MHC class II+ APC, although its Vβ skewing was not found in reactive T cells. Subsequently, we examined the emetic activity of SES and SET. We also studied SElR to determine emetic activity in primates. This toxin was identified in previous studies but was not examined in terms of possession of emetic activity for primates. rSES induced emetic reactions in two of four monkeys at a dose of 100 μg/kg within 5 h of intragastric administration. In one monkey, rSET induced a delayed reaction (24 h postadministration) at a dose of 100 μg/kg, and in the other one, the reaction occurred 5 days postadministration. rSElR induced a reaction in two of six animals within 5 h at 100 μg/kg. On this basis, we speculate that the causative toxins of vomiting in the Fukuoka case are SES and SER. Additionally, SES, SER, and SET also induced emesis in house musk shrews as in the monkeys.

scholarly journals Activated Human T Cells Accomplish MHC Class II Expression Through T Cell-Specific Occupation of Class II Transactivator Promoter III

2002 ◽  
Vol 168 (2) ◽  
pp. 763-770 ◽  
Author(s):  
Tjadine M. Holling ◽  
Nienke van der Stoep ◽  
Edwin Quinten ◽  
Peter J. van den Elsen
Keyword(s):  
T Cells ◽  
T Cell ◽  
Mhc Class Ii ◽  
Class Ii ◽  
Class Ii Transactivator ◽  
Human T Cells ◽  
Specific Occupation

Characterization of Monoclonal Antibodies Against Cell Surface Molecules Associated with Cytotoxic Activity of Natural and Activated Killer Cells and Cloned CTL Lines

Hybridoma ◽  
1983 ◽  
Vol 2 (4) ◽  
pp. 423-437 ◽  
Author(s):  
HERGEN SPITS ◽  
GERRIT KEIZER ◽  
JANNIE BORST ◽  
COX TERHORST ◽  
ANNEMARIE HEKMAN ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Cell Surface ◽  
Cytotoxic Activity ◽  
Cell Surface Molecules ◽  
Killer Cells ◽  
Surface Molecules

Epithelial cells expressing aberrant MHC class II determinants can present antigen to cloned human T cells

Nature ◽  
1984 ◽  
Vol 312 (5995) ◽  
pp. 639-641 ◽  
Author(s):  
Marco Londei ◽  
Jonathan R. Lamb ◽  
Gian Franco Bottazzo ◽  
Marc Feldmann
Keyword(s):  
T Cells ◽  
Epithelial Cells ◽  
Mhc Class Ii ◽  
Class Ii ◽  
Human T Cells

scholarly journals Metalloproteinase-mediated release of human Fas ligand.

1995 ◽  
Vol 182 (6) ◽  
pp. 1777-1783 ◽  
Author(s):  
N Kayagaki ◽  
A Kawasaki ◽  
T Ebata ◽  
H Ohmoto ◽  
S Ikeda ◽  
...  
Keyword(s):  
T Cells ◽  
Monoclonal Antibodies ◽  
Cell Surface ◽  
Fas Ligand ◽  
Integral Membrane Protein ◽  
Human T Cells ◽  
Human Fas Ligand ◽  
Soluble Fasl ◽  
Membrane Type ◽  
Necrosis Factor

Fas ligand (FasL) is a type II integral membrane protein homologous with tumor necrosis factor (TNF). Recent studies indicate that TNF is processed to yield the soluble cytokine by metalloproteinases at the cell surface of activated macrophages and T cells. In the present study, we investigated whether FasL is also released by metalloproteinases. Treatment with hydroxamic acid inhibitors of matrix metalloproteinases specifically led to accumulation of membrane-type FasL (p40) on the surface of human FasL cDNA transfectants and activated human T cells, as estimated by surface immunofluorescence and immunoprecipitation with newly established anti-human FasL monoclonal antibodies. This surface accumulation of mFasL was associated with the decrease of soluble FasL (p27) in the supernatant as estimated by quantitative ELISA and immunoprecipitation with anti-human FasL monoclonal antibodies. These results indicate that human FasL is efficiently released from the cell surface by metalloproteinases like TNF.

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