A soluble divalent class I MHC/IgG1 fusion protein activates CD8+ T cells in vivo

Carey, Brenna; DeLay, Monica; Strasser, Jane E.; Chalk, Claudia; Dudley-McClain, Kristen L.; Milligan, Gregg N.; Brunner, Hermine I.; Thornton, Sherry; Hirsch, Raphael

doi:10.1016/j.clim.2005.02.013

Cited by 8 publications

(18 citation statements)

References 78 publications

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“…Porto mediated by T cell impairment of target cell lysis by CD8ϩ T cells and down-regulation of interferon-␥ production by CD4ϩ T cells (16). However, Hirsch et al observed H-2K b / IgG1 successfully induces Ag-specific T cell activation in vitro and in vivo, and retards tumor growth (33,15). The rational explanation to this paradox would be the ability of the dimer to bind to FcR.…”

Section: Discussionmentioning

confidence: 94%

Peptide-Dependent Inhibition of Alloreactive T-Cell Response by Soluble Divalent HLA-A2/IgG Molecule In Vitro

Weng

Zhong²,

Liang³

et al. 2007

Transplantation

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Section: Discussionmentioning

confidence: 94%

Peptide-Dependent Inhibition of Alloreactive T-Cell Response by Soluble Divalent HLA-A2/IgG Molecule In Vitro

Weng

Zhong²,

Liang³

et al. 2007

Transplantation

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“…Carey et al [40] have shown that divalent MHC-Ig fusion proteins activate T cells in vitro and in vivo. They employed immobilized dimers in their in vitro studies which allowed for TCR cross-linking while they utilized LPS to induce CD4 + T cells and up-regulate co-stimulatory molecules in their in vivo studies.…”

Section: Fig 3: a Diagrammatic Representation Of Mhci-ig Dimersmentioning

confidence: 99%

“…A similar molecule was shown to have the ability to attach TCR ligands to the cells bearing FcRI, such as Monocytes [43]. Other similar strategies have been reported to generate nominal, single epitope-specific CTLs [40,44]. In addition, Carey et al [40] explored the feasibility of these strategies to generate allo-restricted, peptide specific CTLs.…”

Section: Fig 3: a Diagrammatic Representation Of Mhci-ig Dimersmentioning

confidence: 99%

“…Other similar strategies have been reported to generate nominal, single epitope-specific CTLs [40,44]. In addition, Carey et al [40] explored the feasibility of these strategies to generate allo-restricted, peptide specific CTLs. After in vitro co-culture, dimer-loaded HLA-A2-ve monocytes were seen to promote autologous PBLs proliferation, and the expanded CD8 + T cells showed peptide/HLA-A2-specific cytotoxicity.…”

Section: Fig 3: a Diagrammatic Representation Of Mhci-ig Dimersmentioning

confidence: 99%

“…They can be fused to Ig molecules and multimerized using protein A thereby forming MHC-Ig tetramers. Alternatively, they can be fused to an enzymatic biotinylation site (Bir) followed by fluorochrome conjugated streptavidin coupling to form MHC-Bir tetramers [27,40,59]. Those of MHC class I in origin interact with CD8 + T cells while those of MHC class II in origin interact with CD4 + T cells thereby allowing for the identification and subsequent isolation and/or characterization of antigen specific CD8 + or CD4 + T cells respectively.…”

Section: Mhc Tetramersmentioning

confidence: 99%

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MHC-Ig Dimers: The next Frontier in Transplantation Immunology

Wigina

Jeza

2015

Int Jour of Biomed Res

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Organ transplantation offers hope to a variety of patients with terminal functioning organs and tissues. This is currently made possible by administration of general immunosuppressive drugs. To date, inducing tolerance to allografts has become the holy grail of every transplantation immunologist. In effect, there has been a great deal of research aiming to come up with alternative therapeutic mechanisms that would allow one to do away with or reduce the amount of general immunosuppressive drugs used either at the induction, maintenance, or both phases. It has been shown in recent years that MHC-Ig dimers can induce suppression of alloresponsive T cells in a donor specific fashion. Consequently, MHC-Ig fusion proteins are currently forming the next field for exploitation which is great progress in transplantation immunology since the discovery of the first immunosuppressive drugs in terms of inducing tolerance to transplanted organs and tissues. This review aims to discuss this progress.

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MHC‐Ig induces memory T cell formationin vivoand inhibits tumour growth

Schütz¹,

Zoso

Peng

et al. 2014

Immunity, Inflammation and Disease

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Induction of a T cell mediated immune response is critical for the eradication of viral infections and tumours. Soluble peptide-loaded major histocompatibility complex-Ig (pep−MHC-Ig) have been shown to bind their cognate ligands, T cell receptor, with high affinity, and are successfully used to visualize antigen-specific T cells. Furthermore, immobilized pep−MHC-Ig can activate and expand antigen-specific T cells in vitro and in vivo. In this study, we investigate the use of pep−MHC-Ig as a potential strategy to modulate antigen specific T cell immune responses in vivo. SIY−Kb-Ig immunization, together with the pre-activation by an anti-CD40 monoclonal antibody, is able to stimulate a strong expansion of adoptively transferred 2C transgenic T cells and the formation of long term antigen-specific memory T cells. In addition, mechanistic studies show that the pep−MHC-Ig molecules directly activate T cells in vivo without requiring uptake and reprocessing by antigen-presenting cells. Furthermore, B6 mice immunized with pep−MHC-Ig molecules inhibit tumour growth in a B16-SIY melanoma prevention model. Thus, soluble pep−MHC-Ig molecules represent a powerful tool for active immunotherapy.

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A soluble divalent class I MHC/IgG1 fusion protein activates CD8+ T cells in vivo

Cited by 8 publications

References 78 publications

Peptide-Dependent Inhibition of Alloreactive T-Cell Response by Soluble Divalent HLA-A2/IgG Molecule In Vitro

Peptide-Dependent Inhibition of Alloreactive T-Cell Response by Soluble Divalent HLA-A2/IgG Molecule In Vitro

MHC-Ig Dimers: The next Frontier in Transplantation Immunology

MHC‐Ig induces memory T cell formationin vivoand inhibits tumour growth

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