Turning Tregs into class I suppressors

Blood ◽  
2012 ◽  
Vol 119 (15) ◽  
pp. 3373-3374 ◽  
Author(s):  
Terrence L. Geiger
Keyword(s):  
T Cells ◽  
T Cell ◽  
Regulatory T Cells ◽  
Mhc Class I ◽  
T Cell Receptors ◽  
Class I ◽  
Cell Receptors ◽  
Tcr Affinity

In this issue of Blood, Plesa et al demonstrate that human Foxp3+ regulatory T cells can be redirected using MHC class I–restricted T-cell receptors (TCRs), showing a surprising lack of correlation of TCR affinity and their suppressive potency.1

scholarly journals MHC Class I Bound to an Immunodominant Theileria parva Epitope Demonstrates Unconventional Presentation to T Cell Receptors

2010 ◽  
Vol 6 (10) ◽  
pp. e1001149 ◽  
Author(s):  
Isabel K. Macdonald ◽  
Maria Harkiolaki ◽  
Lawrence Hunt ◽  
Timothy Connelley ◽  
A. Victoria Carroll ◽  
...  
Keyword(s):  
T Cell ◽  
Mhc Class I ◽  
T Cell Receptors ◽  
Class I ◽  
Theileria Parva ◽  
Cell Receptors

scholarly journals Peptide–MHC Binding Reveals Conserved Allosteric Sites in MHC Class I- and Class II-Restricted T Cell Receptors (TCRs)

2020 ◽  
Vol 432 (24) ◽  
pp. 166697 ◽  
Author(s):  
Yanan He ◽  
Pragati Agnihotri ◽  
Sneha Rangarajan ◽  
Yihong Chen ◽  
Melissa C. Kerzic ◽  
...  
Keyword(s):  
T Cell ◽  
Mhc Class I ◽  
T Cell Receptors ◽  
Class Ii ◽  
Class I ◽  
Cell Receptors ◽  
Allosteric Sites

scholarly journals Immunoglobulins, MHC and T Cell receptors genes in Cetaceans

2020 ◽  
Author(s):  
Francisco Gambón-Deza
Keyword(s):  
T Cell ◽  
Mhc Class I ◽  
Marine Environment ◽  
T Lymphocyte ◽  
T Cell Receptors ◽  
Immunoglobulin M ◽  
Class I ◽  
Cell Receptors ◽  
Vh Genes ◽  
Lymphocyte Receptors

AbstractCetaceans correspond to mammals that have returned to the marine environment. Adaptive changes are very significant with the conversion of the limbs into flippers. It is studied the changes that have occurred in immunoglobulins, MHC class I and II and T cell receptors genes. Constant regions of immunoglobulins are similar to those of the rest of mammals. An exception is the IgD gene, which is composed of three CH domains but CH1 similar to CH1 of immunoglobulin M. In the IGHV locus, it exist a decrease in the number of VH genes with the absence of genes within Clan I. The number of Vλ genes is greater than that of Vκ. In the genes for T lymphocyte receptors, it exists a decrease in the number of Vα genes with loss of significant clades and subclades. In Vβ and Vγ, there is also the loss of clades. These declines of Vα, Vβ and Vγ are not present Artiodactyla, and they are specific to Cetaceans. In MHC present tree evolutive lines of class I genes. These species have DQ, DR, DO and DM genes, but they are no present DP genes.

Impact of Regulatory T Cells on Antigen Specific T Cell Response Using Recombinant Chimeric T Cell Receptors In Vivo.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5475-5475
Author(s):  
David M. Kofler ◽  
Markus Chmielewski ◽  
Heike Koehler ◽  
Tobias Riet ◽  
Patrick Schmidt ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Regulatory T Cells ◽  
Tumor Cells ◽  
T Cell Receptors ◽  
Cell Response ◽  
Effector T Cells ◽  
T Cell Response ◽  
Cell Receptors

Abstract Recombinant T cell receptors with defined specificity against tumor cells are a promising experimental approach in the elimination of residual leukemia and lymphoma cells. It is so far unresolved whether regulatory T cells with suppressor activities impair the efficiency of cytolytic T cells grafted with a recombinant immunoreceptor. The frequency of regulatory T cells is highly increased in tumor patients and their suppressive function seems to play a role in the fail of an autologous T cell response against the malignant cells. In this study we analyzed the antigen-triggered, specific activation of receptor grafted T cells in the presence or absence of regulatory CD4+CD25high T cells. CD3+ T cells were grafted with CEA-specific immunoreceptors containing the CD3-zeta signaling domain for T cell activation. Co-cultivation of receptor grafted effector T cells together with regulatory T cells repressed proliferation of the effector cells and decreased IL-2 secretion. Secretion of IFN-gamma and IL-10 was not impaired. Interestingly, the cytotoxicity of grafted effector T cells towards CEA-expressing tumor cells was not impaired by regulatory T cells in vitro. To evaluate the relevance in vivo, we used a Crl:CD1 Nu/Nu mouse model to assess growth of CEA+ tumor cells in the presence of receptor grafted effector T cells and of regulatory T cells. Mice inoculated with tumor cells together with CD3+ effector T cells without immunoreceptor and regulatory T cells developed earlier tumors with faster growth kinetics compared to mice that were inoculated with tumor cells, CD3+ T cells and CD4+CD25- control T cells. Using effector T cells that were equipped with a recombinant CEA-specific CD3-zeta immunoreceptor, 2 of 5 mice developed a tumor in the presence of regulatory T cells while none of the mice developed a tumor in the absence of regulatory T cells. Taken together, regulatory T cells obviously impair an antigen-specific, anti-tumor T cell attack in vivo. This seems to be due to repression of proliferation of the effector T cells and not to diminished cytotoxicity. These findings have major impact on the design of clinical studies involving adoptively transferred effector T cells.

HLAs, TCRs, and KIRs, a Triumvirate of Human Cell-Mediated Immunity

2020 ◽  
Vol 89 (1) ◽  
pp. 717-739 ◽  
Author(s):  
Zakia Djaoud ◽  
Peter Parham
Keyword(s):  
T Cells ◽  
T Cell ◽  
Nk Cells ◽  
T Cell Receptors ◽  
Hla Class I ◽  
Class Ii ◽  
Class I ◽  
Antigenic Specificity ◽  
Class I Mhc ◽  
Cell Receptors

In all human cells, human leukocyte antigen (HLA) class I glycoproteins assemble with a peptide and take it to the cell surface for surveillance by lymphocytes. These include natural killer (NK) cells and γδ T cells of innate immunity and αβ T cells of adaptive immunity. In healthy cells, the presented peptides derive from human proteins, to which lymphocytes are tolerant. In pathogen-infected cells, HLA class I expression is perturbed. Reduced HLA class I expression is detected by KIR and CD94:NKG2A receptors of NK cells. Almost any change in peptide presentation can be detected by αβ CD8+ T cells. In responding to extracellular pathogens, HLA class II glycoproteins, expressed by specialized antigen-presenting cells, present peptides to αβ CD4+ T cells. In comparison to the families of major histocompatibility complex (MHC) class I, MHC class II and αβ T cell receptors, the antigenic specificity of the γδ T cell receptors is incompletely understood.

scholarly journals Advanced Approaches in Immunotherapy for the Treatment of Type 1 Diabetes Mellitus

EMJ Diabetes ◽  
2020 ◽  
Author(s):  
Bryan Ceballos ◽  
Michael Alexander ◽  
Jonathan R. T. Lakey
Keyword(s):  
Diabetes Mellitus ◽  
T Cells ◽  
Type 1 Diabetes ◽  
Immune System ◽  
T Cell ◽  
Regulatory T Cells ◽  
Type 1 Diabetes Mellitus ◽  
T Cell Receptors ◽  
Cell Receptors

The cure for Type 1 diabetes mellitus (T1DM) is likely to require an effective strategy for suppressing or evading the immune system. When considering curative treatments, it is almost inevitable to consider novel ways of inducing tolerogenicity to insulin-producing β cells. While the main mechanism of achieving tolerogenicity is restoring regulatory T cell (CD4+CD25+Fox3+) to effector T-cell (CD4+Fox3-) homeostasis, the means of achieving this are multifarious. The advent of a glucocorticoid-free immunosuppressive regimen was an early indication of how immunotherapeutics affect β-cell function. As newer biologics are developed, suppressing the immune system continues to become more specific and dynamic. An ever-evolving field of immunology has shifted the paradigm of how T1DM is understood, and the repurposing of T-cell-based biotechnology has the potential to change the way that it is treated. Regulatory T cells can be bioengineered to express T-cell receptors with affinity for peptide–human leukocyte antigen complexes that are frequently encountered in T1DM. Exosomes with embedded T-cell receptors can be isolated from regulatory T cells for use as an off-the-shelf therapy.

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