scholarly journals Btn2a2, a T cell immunomodulatory molecule coregulated with MHC class II genes

2016 ◽  
Vol 213 (2) ◽  
pp. 177-187 ◽  
Author(s):  
Kerstin Sarter ◽  
Elisa Leimgruber ◽  
Florian Gobet ◽  
Vishal Agrawal ◽  
Isabelle Dunand-Sauthier ◽  
...  
Keyword(s):  
T Cell ◽  
Mhc Class Ii ◽  
Class Ii ◽  
Cell Mediated Immunity ◽  
Factor X ◽  
Cell Immunity ◽  
Cell Induction ◽  
Genes Encoding ◽  
Inhibitory Molecule ◽  
Antigen Presenting

Evidence has recently emerged that butyrophilins, which are members of the extended B7 family of co-stimulatory molecules, have diverse functions in the immune system. We found that the human and mouse genes encoding butyrophilin-2A2 (BTN2A2) are regulated by the class II trans-activator and regulatory factor X, two transcription factors dedicated to major histocompatibility complex class II expression, suggesting a role in T cell immunity. To address this, we generated Btn2a2-deficient mice. Btn2a2−/− mice exhibited enhanced effector CD4+ and CD8+ T cell responses, impaired CD4+ regulatory T cell induction, potentiated antitumor responses, and exacerbated experimental autoimmune encephalomyelitis. Altered immune responses were attributed to Btn2a2 deficiency in antigen-presenting cells rather than T cells or nonhematopoietic cells. These results provide the first genetic evidence that BTN2A2 is a co-inhibitory molecule that modulates T cell–mediated immunity.

scholarly journals Small amounts of superantigen, when presented on dendritic cells, are sufficient to initiate T cell responses.

1993 ◽  
Vol 178 (2) ◽  
pp. 633-642 ◽  
Author(s):  
N Bhardwaj ◽  
J W Young ◽  
A J Nisanian ◽  
J Baggers ◽  
R M Steinman
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
Dendritic Cell ◽  
Mhc Class Ii ◽  
Cell Receptor ◽  
Class Ii ◽  
Cell Mediated Immunity ◽  
Quiescent T Cells ◽  
Antigen Presenting

Dendritic cells are potent antigen-presenting cells for several primary immune responses and therefore provide an opportunity for evaluating the amounts of cell-associated antigens that are required for inducing T cell-mediated immunity. Because dendritic cells express very high levels of major histocompatibility complex (MHC) class II products, it has been assumed that high levels of ligands bound to MHC products ("signal one") are needed to stimulate quiescent T cells. Here we describe quantitative aspects underlying the stimulation of human blood T cells by a bacterial superantigen, staphylococcal enterotoxin A (SEA). The advantages of superantigens for quantitative studies of signal one are that these ligands: (a) engage MHC class II and the T cell receptor but do not require processing; (b) are efficiently presented to large numbers of quiescent T cells; and (c) can be pulsed onto dendritic cells before their application to T cells. Thus one can relate amounts of dendritic cell-associated SEA to subsequent lymphocyte stimulation. Using radioiodinated SEA, we noted that dendritic cells can bind 30-200 times more superantigen than B cells and monocytes. Nevertheless, this high SEA binding does not underlie the strong potency of dendritic cells to present antigen to T cells. Dendritic cells can sensitize quiescent T cells, isolated using monoclonals to appropriate CD45R epitopes, after a pulse of SEA that occupies a maximum of 0.1% of surface MHC class II molecules. This corresponds to an average of 2,000 molecules per dendritic cell. At these low doses of bound SEA, monoclonal antibodies to CD3, CD4, and CD28 almost completely block T cell proliferation. In addition to suggesting new roles for MHC class II on dendritic cells, especially the capture and retention of ligands at low external concentrations, the data reveal that primary T cells can generate a response to exceptionally low levels of signal one as long as these are delivered on dendritic cells.

scholarly journals SpeS: A Novel Superantigen and Its Potential as a Vaccine Adjuvant against Strangles

2020 ◽  
Vol 21 (12) ◽  
pp. 4467
Author(s):  
C. Coral Dominguez-Medina ◽  
Nicola L. Rash ◽  
Sylvain Robillard ◽  
Carl Robinson ◽  
Androulla Efstratiou ◽  
...  
Keyword(s):  
T Cell ◽  
Mhc Class Ii ◽  
Surface Protein ◽  
Cell Receptor ◽  
Class Ii ◽  
Surface Proteins ◽  
Binding Motif ◽  
Binding Properties ◽  
Antigen Presenting

Bacterial superantigens (sAgs) are powerful activators of the immune response that trigger unspecific T cell responses accompanied by the release of proinflammatory cytokines. Streptococcus equi (S. equi) and Streptococcus zooepidemicus (S. zooepidemicus) produce sAgs that play an important role in their ability to cause disease. Strangles, caused by S. equi, is one of the most common infectious diseases of horses worldwide. Here, we report the identification of a new sAg of S. zooepidemicus, SpeS, and show that mutation of the putative T cell receptor (TCR)-binding motif (YAY to IAY) abrogated TCR-binding, whilst maintaining interaction with major histocompatibility complex (MHC) class II molecules. The fusion of SpeS and SpeSY39I to six S. equi surface proteins using two different peptide linkers was conducted to determine if MHC class II-binding properties were maintained. Proliferation assays, qPCR and flow cytometry analysis showed that SpeSY39I and its fusion proteins induced less mitogenic activity and interferon gamma expression when compared to SpeS, whilst retaining Antigen-Presenting Cell (APC)-binding properties. Our data suggest that SpeSY39I-surface protein fusions could be used to direct vaccine antigens towards antigen-presenting cells in vivo with the potential to enhance antigen presentation and improve immune responses.

scholarly journals Immortalized dendritic cell line fully competent in antigen presentation initiates primary T cell responses in vivo.

1993 ◽  
Vol 178 (6) ◽  
pp. 1893-1901 ◽  
Author(s):  
P Paglia ◽  
G Girolomoni ◽  
F Robbiati ◽  
F Granucci ◽  
P Ricciardi-Castagnoli
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
Dendritic Cell ◽  
Cell Line ◽  
Mhc Class Ii ◽  
Class Ii ◽  
Gm Csf ◽  
Antigen Presenting

Dendritic cells (DC) can provide all the known costimulatory signals required for activation of unprimed T cells and are the most efficient and perhaps the critical antigen presenting cells in the induction of primary T cell-mediated immune responses. It is now shown that mouse cell lines with many of the features of DC can be generated using the MIB phi 2-N11 retroviral vector transducing a novel envAKR-mycMH2 fusion gene. The immortalized dendritic cell line (CB1) displays most of the morphologic, immunophenotypic, and functional attributes of DC, including constitutive expression of major histocompatibility complex (MHC) class II molecules, costimulatory molecules B7/BB1, heat stable antigen, intracellular adhesion molecule 1, and efficient antigen-presenting ability. Granulocyte/macrophage colony-stimulating factor (GM-CSF) proved to be effective in increasing MHC class II molecule expression and in enhancing presentation of native protein antigens. In comparison with macrophages, CB1 dendritic cells did not exhibit phagocytic and chemotactic activity in response to various stimuli and lipopolysaccharide activation was ineffective in inducing tumor necrosis factor alpha or interleukin 1 beta production. CB1 cells, pulsed with haptens in vitro and injected into naive mice were able to induce delayed-type hypersensitivity responses, further increased with pretreatment with GM-CSF, indicating that these cells may represent an immature, rather than a mature DC. The ability of CB1 to prime T cells in vivo could provide a tool to design novel immunization strategies.

scholarly journals MHC Class II–Restricted Antigen Presentation by Plasmacytoid Dendritic Cells Drives Proatherogenic T Cell Immunity

Circulation ◽  
2014 ◽  
Vol 130 (16) ◽  
pp. 1363-1373 ◽  
Author(s):  
Andrew P. Sage ◽  
Deirdre Murphy ◽  
Pasquale Maffia ◽  
Leanne M. Masters ◽  
Suleman R. Sabir ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
Antigen Presentation ◽  
Mhc Class Ii ◽  
Class Ii ◽  
Plasmacytoid Dendritic Cells ◽  
T Cell Immunity ◽  
Cell Immunity

scholarly journals CD8α+ and CD11b+ Dendritic Cell-Restricted MHC Class II Controls Th1 CD4+ T Cell Immunity

2003 ◽  
Vol 171 (10) ◽  
pp. 5077-5084 ◽  
Author(s):  
Maria P. Lemos ◽  
Lian Fan ◽  
David Lo ◽  
Terri M. Laufer
Keyword(s):  
T Cell ◽  
Dendritic Cell ◽  
Mhc Class Ii ◽  
Class Ii ◽  
T Cell Immunity ◽  
Cd4 T Cell ◽  
Cell Immunity

scholarly journals Host MHC class II+ antigen-presenting cells and CD4 cells are required for CD8-mediated graft-versus-leukemia responses following delayed donor leukocyte infusions

Blood ◽  
2006 ◽  
Vol 108 (6) ◽  
pp. 2106-2113 ◽  
Author(s):  
Ronjon Chakraverty ◽  
Hyeon-Seok Eom ◽  
Jessica Sachs ◽  
Jennifer Buchli ◽  
Pete Cotter ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Mhc Class Ii ◽  
Antigen Presenting Cells ◽  
Class Ii ◽  
Cd4 T Cell ◽  
Graft Versus Host ◽  
Graft Versus Leukemia ◽  
T Cell Help ◽  
Antigen Presenting

Abstract Following bone marrow transplantation, delayed donor leukocyte infusions (DLIs) can induce graft-versus-leukemia (GVL) effects without graft-versus-host disease (GVHD). These antitumor responses are maximized by the presence of host hematopoietic antigen-presenting cells (APCs) at the time of DLI. Using a tumor-protection model, we demonstrate here that GVL activity following administration of DLIs to established mixed chimeras is dependent primarily on reactivity to allogeneic MHC antigens rather than minor histocompatibility or tumor-associated antigens. CD8+ T-cell–dependent GVL responses against an MHC class II–negative tumor following delayed DLI require CD4+ T-cell help and are reduced significantly when host APCs lack MHC class II expression. CD4+ T cells primed by host APCs were required for maximal expansion of graft-versus-host reactive CD8+ T cells but not their synthesis of IFN-γ. In contrast, the GVL requirement for CD4+ T-cell help was bypassed almost completely when DLI was administered to freshly irradiated recipients, indicating that the host environment is a major factor influencing the cellular mechanisms of GVL.

scholarly journals Trypanosoma cruzi Infection Modulates In Vivo Expression of Major Histocompatibility Complex Class II Molecules on Antigen-Presenting Cells and T-Cell Stimulatory Activity of Dendritic Cells in a Strain-Dependent Manner

2003 ◽  
Vol 71 (3) ◽  
pp. 1194-1199 ◽  
Author(s):  
Catalina D. Alba Soto ◽  
Gerardo A. Mirkin ◽  
Maria E. Solana ◽  
Stella M. González Cappa
Keyword(s):  
Major Histocompatibility Complex ◽  
T Cell ◽  
Mhc Class Ii ◽  
Class Ii ◽  
Peritoneal Macrophages ◽  
Dependent Manner ◽  
Histocompatibility Complex ◽  
Antigen Presenting ◽  
Strain Dependent

ABSTRACT A striking feature of Chagas' disease is the diversity of clinical presentations. Such variability may be due to the heterogeneity among Trypanosoma cruzi isolates or to the host immune response. Employing two strains which differ in their virulence, we investigated the effect of in vivo infection on professional antigen-presenting cells (APC). Acute infection with the virulent RA strain downregulated the expression of major histocompatibility complex (MHC) class II on splenic dendritic cells (DC) and inhibited its induction on peritoneal macrophages and splenic B cells. It also impaired the ability of DC to prime allogeneic T cells and to form homotypic clusters, suggesting a low maturation state of these cells. In contrast, the low-virulence K98 strain maintained the expression of MHC class II on DC or stimulated it on peritoneal macrophages and B cells and preserved DC's T-cell priming capacity and homotypic clustering. DC from RA-infected mice elicited a lower activation of T. cruzi-specific T-cell proliferation than those from K98-infected mice. APC from RA-infected mice that reached the chronic phase of infection restored MHC class II levels to those found in K98-infected mice and upregulated costimulatory molecules expression, suggesting that the immunosuppression caused by this strain is only transient. Taken together, the results indicate that in vivo infection with T. cruzi modulates APC functionality and that this is accomplished in a strain-dependent manner.

scholarly journals Understanding Delayed T-Cell Priming, Lung Recruitment, and Airway Luminal T-Cell Responses in Host Defense against Pulmonary Tuberculosis

2012 ◽  
Vol 2012 ◽  
pp. 1-13 ◽  
Author(s):  
Christopher R. Shaler ◽  
Carly Horvath ◽  
Rocky Lai ◽  
Zhou Xing
Keyword(s):  
T Cell ◽  
Pulmonary Tuberculosis ◽  
Mhc Class Ii ◽  
Legionella Pneumophila ◽  
Effector T Cells ◽  
Health Concern ◽  
Cell Responses ◽  
Cell Immunity ◽  
Causative Bacterium ◽  
Antigen Presenting

Mycobacterium tuberculosis(M.tb), the causative bacterium of pulmonary tuberculosis (TB), is a serious global health concern. Central toM.tbeffective immune avoidance is its ability to modulate the early innate inflammatory response and prevent the establishment of adaptive T-cell immunity for nearly three weeks. When compared with other intracellular bacterial lung pathogens, such asLegionella pneumophila, or even closely related mycobacterial species such asM. smegmatis, this delay is astonishing. Customarily, the alveolar macrophage (AM) acts as a sentinel, detecting and alerting surrounding cells to the presence of an invader. However, in the case ofM.tb,this may be impaired, thus delaying the recruitment of antigen-presenting cells (APCs) to the lung. Upon uptake by APC populations,M.tbis able to subvert and delay the processing of antigen, MHC class II loading, and the priming of effector T cell populations. This delay ultimately results in the deferred recruitment of effector T cells to not only the lung interstitium but also the airway lumen. Therefore, it is of upmost importance to dissect the mechanisms that contribute to the delayed onset of immune responses followingM.tbinfection. Such knowledge will help design the most effective vaccination strategies against pulmonary TB.

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