Recombinant dimeric MHC antigens protect cardiac allografts from rejection and visualize alloreactive T cells

Fried, Ari J.; Berg, Martina; Sharma, Bhavna; Bonde, Sabrina; Zavazava, Nicholas

doi:10.1189/jlb.0205078

Cited by 7 publications

(7 citation statements)

References 29 publications

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“…Over the last two decades induction of T cell immunity utilizing soluble pepÀ MHC-Ig in vivo has been a challenging approach resulting in different outcomes depending on the experimental set up and treatment protocol [15,17,20,21].…”

Section: Discussionmentioning

confidence: 99%

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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Section: Discussionmentioning

confidence: 99%

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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“…Recently, soluble ligands for TCRs in multimeric form have been developed to target Agspecific T cells with increased affinity (30,31). 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).…”

Section: Discussionmentioning

confidence: 97%

“…Recently, soluble ligands for TCRs consisting of engineered MHC molecules in multimeric form have been developed to target Ag-specific T cells (14,15). Like monoclonal antibodies (mAbs) directed against the TCR/CD3 complex, soluble bivalent peptide-MHC molecules are capable of delivering a signal through the TCR and result in transduction of a unique signal that leads to immune dysfunction and tolerance induction (16,17).…”

mentioning

confidence: 99%

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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“…Fried et al reported in 2005 that rat RT1.A-Fc dimers were able to prolong the survival time of heart grafts, suggesting the utility of soluble MHC dimers for inhibiting transplant rejection. pMHC dimer may therefore be useful for inhibiting transplant rejection (188).…”

Section: Role Of Soluble Donor Mhc-i Moleculesmentioning

confidence: 99%

The Role of Diverse Liver Cells in Liver Transplantation Tolerance

et al. 2020

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Liver transplantation is the ideal treatment approach for a variety of end-stage liver diseases. However, lifelong , systemic immunosuppressive treatment after transplantation is required to prevent rejection and graft loss, which is associated with severe side effects, although liver allograft is considered more tolerogenic. Therefore, understanding the mechanism underlying the unique immunologically privileged liver organ is valuable for transplantation management and autoimmune disease treatment. The unique hepatic acinus anatomy and a complex cellular network constitute the immunosuppressive hepatic microenvironment, which are responsible for the tolerogenic properties of the liver. The hepatic microenvironment contains a variety of hepatic-resident immobile non-professional antigen-presenting cells, including hepatocytes, liver sinusoidal endothelial cells, Kupffer cells, and hepatic stellate cells, that are insufficient to optimally prime T cells locally and lead to the removal of alloreactive T cells due to the low expression of major histocompatibility complex (MHC) molecules, costimulatory molecules and proinflammatory cytokines but a rather high expression of coinhibitory molecules and anti-inflammatory cytokines. Hepatic dendritic cells (DCs) are generally immature and less immunogenic than splenic DCs and are also ineffective in priming naïve allogeneic T cells via the direct recognition pathway in recipient secondary lymphoid organs. Although natural killer cells and natural killer T cells are reportedly associated with liver tolerance, their roles in liver transplantation are multifaceted and need to be further clarified. Under these circumstances, T cells are prone to clonal deletion, clonal anergy and exhaustion, eventually leading to tolerance. Other proposed liver tolerance mechanisms, such as soluble donor MHC class I molecules, passenger leukocytes theory and a high-load antigen effect, have also been addressed. We herein comprehensively review the current evidence implicating the tolerogenic properties of diverse liver cells in liver transplantation tolerance.

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Recombinant dimeric MHC antigens protect cardiac allografts from rejection and visualize alloreactive T cells

Cited by 7 publications

References 29 publications

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

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

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

The Role of Diverse Liver Cells in Liver Transplantation Tolerance

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