scholarly journals Expression of Major Histocompatibility Complex Class II and CD80 by Gingival Epithelial Cells Induces Activation of CD4+ T Cells in Response to Bacterial Challenge

2005 ◽  
Vol 73 (2) ◽  
pp. 1044-1051 ◽  
Author(s):  
Takashi Matsuyama ◽  
Toshihisa Kawai ◽  
Yuichi Izumi ◽  
Martin A Taubman
Keyword(s):  
T Cells ◽  
Epithelial Cells ◽  
Mhc Class Ii ◽  
Class Ii ◽  
Bacterial Antigen ◽  
Histocompatibility Complex ◽  
Hla Dr ◽  
Gingival Epithelial Cells ◽  
Ifn Γ ◽  
Clone Cells

ABSTRACT HLA-DR (major histocompatibility complex [MHC] class II) is often expressed by epithelial cells in gingival tissues with periodontal disease but not by cells in healthy gingival tissues. Confocal microscopic analyses revealed that gingival epithelial cells (GEC) from tissue with periodontal disease express both HLA-DR and B7-1 (CD80) costimulatory molecules. Rat GEC lines were established to elucidate the possible role of MHC class II and B7-1 expression by GEC. Stimulation of a rat GEC line with gamma interferon (IFN-γ) induced the expression of MHC class II, whereas the cell line constitutively expressed B7-1 costimulatory molecules as determined by reverse transcription-PCR and flow cytometry. Actinobacillus actinomycetemcomitans Omp29-specific CD4+ Th1 clone cells proliferated in response to pretreatment of GEC with fixed A. actinomycetemcomitans and IFN-γ. However, the Th1 cells did not respond to pretreatment of GEC with the bacteria alone or IFN-γ alone. The activation of Th1 clone cells induced by the GEC was inhibited by antibody to MHC class II or by CTLA4 immunoglobulin (CTLA4-Ig). Lymph node T cells did not demonstrate superantigen activity to A. actinomycetemcomitans, although both lymph node T cells and Th1 clone cells were sensitive to superantigen activity of staphylococcal enterotoxin A as cultured in the presence of IFN-γ-treated GEC. These results suggested that GEC can take up bacterial antigen and consequently process and present the bacterial antigen to CD4+ T cells by MHC class II in conjunction with B7 costimulation. GEC appeared to play a role in the adaptive immune response by stimulating antigen-specific CD4+ T cells.

scholarly journals HLA-DR alleles differ in their ability to present staphylococcal enterotoxins to T cells.

1990 ◽  
Vol 172 (3) ◽  
pp. 709-717 ◽  
Author(s):  
A Herman ◽  
G Croteau ◽  
R P Sekaly ◽  
J Kappler ◽  
P Marrack
Keyword(s):  
T Cells ◽  
Mhc Class Ii ◽  
Class Ii ◽  
Human Class ◽  
Staphylococcal Enterotoxins ◽  
Histocompatibility Complex ◽  
Hla Dr ◽  
Specific Manner ◽  
Class Ii Antigens ◽  
Mhc Class Ii Molecules

Staphylococcal enterotoxins (SEs) have been shown to bind to major histocompatibility complex (MHC) class II proteins and stimulate T cells in a V beta-specific manner, and these V beta specificities for various SEs have been well documented in mice and humans. This study was undertaken in order to examine the ability of human class II molecules to present SEs to human and murine T cell hybridomas. Using a panel of transfectants expressing individual HLA class II antigens, we have shown that HLA-DR alleles differ in their ability to bind and present SEs. Since the HLA-DR proteins share a common alpha chain, these results indicate that the polymorphic beta chain plays an important role in SE binding and presentation to T cells. In addition, we have shown that human class II isotypes markedly differ in their ability to present SEs. The results of this study should provide information on the region of MHC class II molecules that interacts with foreign, and perhaps self, super-antigens.

scholarly journals Francisella tularensis Induces Ubiquitin-Dependent Major Histocompatibility Complex Class II Degradation in Activated Macrophages

2009 ◽  
Vol 77 (11) ◽  
pp. 4953-4965 ◽  
Author(s):  
Justin E. Wilson ◽  
Bhuvana Katkere ◽  
James R. Drake
Keyword(s):  
T Cells ◽  
Major Histocompatibility Complex ◽  
T Cell ◽  
Mhc Class Ii ◽  
Francisella Tularensis ◽  
Class Ii ◽  
Activated Macrophages ◽  
Cell Responses ◽  
Histocompatibility Complex ◽  
Ifn Γ

ABSTRACT The intracellular bacterium Francisella tularensis survives and replicates within macrophages, ultimately killing the host cell. Resolution of infection requires the development of adaptive immunity through presentation of F. tularensis antigens to CD4+ and CD8+ T cells. We have previously established that F. tularensis induces macrophage prostaglandin E2 (PGE2) production, leading to skewed T-cell responses. PGE2 can also downregulate macrophage major histocompatibility complex (MHC) class II expression, suggesting that F. tularensis-elicited PGE2 may further alter T-cell responses via inhibition of class II expression. To test this hypothesis, gamma interferon (IFN-γ)-activated reporter macrophages were exposed to supernatants from F. tularensis-infected macrophages, and the class II levels were measured. Exposure of macrophages to infection supernatants results in essentially complete clearance of surface class II and CD86, compromising the macrophage's ability to present antigens to CD4 T cells. Biochemical analysis revealed that infection supernatants elicit ubiquitin-dependent class II downregulation and degradation within intracellular acidic compartments. By comparison, exposure to PGE2 alone only leads to a minor decrease in macrophage class II expression, demonstrating that a factor distinct from PGE2 is eliciting the majority of class II degradation. However, production of this non-PGE2 factor is dependent on macrophage cyclooxygenase activity and is induced by PGE2. These results establish that F. tularensis induces the production of a PGE2-dependent factor that elicits MHC class II downregulation in IFN-γ-activated macrophages through ubiquitin-mediated delivery of class II to lysosomes, establishing another mechanism for the modulation of macrophage antigen presentation during F. tularensis infection.

CD4+ Perforin+ T Cells in B-CLL: MHC Class II Restriction and Anti-Cytomegalovirus Reactivity.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4979-4979
Author(s):  
James Walton ◽  
Keirissa Lawson ◽  
Maria S. Manoussaka ◽  
Amit Nathwani ◽  
Vincent Emory ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Mhc Class Ii ◽  
Cd4 T Cells ◽  
Cell Expansion ◽  
Class Ii ◽  
Cd4 Cells ◽  
Hla Dr ◽  
Ifn Γ ◽  
T Cell Expansion

Abstract Introduction: An expansion of CD4+ T cells expressing perforin (PF) has recently been described in B-CLL and we have previously demonstrated anti-cytomegalovirus (CMV) reactivity within this population (Walton et al; 2004; Blood [ASH annual meeting abstracts] 104:4787). Here we further characterise the anti-CMV response of CD4+PF+ T cells in B-CLL and investigate the role of CMV in CD4+PF+ T cell expansion. Methods: Peripheral blood mononuclear cells (PBMC’s) from 24 untreated B-CLL patients (17 CMV seropositive [SP], 7 CMV seronegative [SN]), 2 SP treated (Campath) patients and 12 healthy age-matched control individuals (8 SP, 4 SN) were fixed, permeabilised and stained with anti-CD4PerCP, anti-IFN-γ-APC and anti-PF-FITC monoclonal antibodies (mABs) (BD). PBMC were cultured for 18 hrs with DOWNE cell lysate (Dade Behring) containing CMV-antigen or lysate alone and with anti-CD28 and anti-CD49d mAbs (BD), in the presence of Brefeldin A (eBiosciences). In blocking experiments PBMC were pre-incubated with anti-HLA DR,DP,DQ mAb (BD) for 1 hour. The CMV specific response was assessed by flow cytometry (Dako Cyan, Summit software) as the percentage of IFN-γ+ cells in PF+ and PF− CD4+ T cell populations. Statistical analysis was performed using the Mann-Whitney U test and Spearman rank correlation. Results: The proportion of CD4+ T cells expressing PF directly ex vivo was significantly higher in SP B-CLL patients (17.5±18.6%) compared to SN patients (2.0±2.3%, p=0.019). In seropositive aged matched controls the percentage of CD4+ cells expressing perforin was positively correlated with the percentage of CMV-reactive CD4+ cells (r=0.976, p<0.01). In contrast, there was no significant correlation in the patient group. However, two patients with relatively large expansions of CD4+PF+ cells (37.7±3.39%) post-Campath treatment had high percentages of CMV-reactive CD4+ cells (10.93±0.62%) compared to SP B-CLL patients (1.34±1.19%) and SP controls (1.31±1.14%), implying Campath related CMV reactivation. The addition of anti-HLA-DR,DP,DQ mAb to patients’ PBMCs, prior to CMV stimulation, led to an 80% (from 3.26% to 0.79%) and 90% (from 3.9% to 0.45%) reduction in the proportion of antigen reactive CD4+ and CD4+PF+ cells respectively. Conclusions: A population of major histocompatibility complex (MHC) class II restricted, CMV reactive, CD4+PF+ T cells exists peripherally, in a large group of CMV SP B-CLL patients. Furthermore, CMV is associated with CD4+PF+ T cell expansion in patients and controls. Our data implies that high numbers of B-CLL cells inhibit anti-viral effector function, leading to increased viral activity and chronic antigenic exposure, potentially driving CD4+PF+ T cell expansion.

scholarly journals Molecular characterization of major histocompatibility complex class II gene expression and demonstration of antigen-specific T cell response indicate a new phenotype in class II-deficient patients.

1995 ◽  
Vol 181 (4) ◽  
pp. 1411-1423 ◽  
Author(s):  
I Hauber ◽  
H Gulle ◽  
H M Wolf ◽  
M Maris ◽  
H Eggenbauer ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
Major Histocompatibility Complex ◽  
B Cells ◽  
Mhc Class Ii ◽  
Class Ii ◽  
Specific Protein ◽  
Histocompatibility Complex ◽  
Hla Dr ◽  
Class Ii Antigens

Major histocompatibility complex (MHC) class II deficiency is an inherited autosomal recessive combined immunodeficiency. The disease is known as bare lymphocyte syndrome (BLS). BLS is characterized by a lack of constitutive MHC class II expression on macrophages and B cells as well as a lack of induced MHC class II expression on cells other than professional antigen-presenting cells (APCs) due to the absence of mRNA and protein of the human leukocyte antigen (HLA) class II molecules, designated HLA-DR, -DQ, and -DP. The defect in gene expression is located at the transcriptional level and affects all class II genes simultaneously. Here we have analyzed transcription and protein expression of class II antigens in Epstein-Barr virus (EBV)-transformed B lymphoblastoid cell lines and mononuclear cells (MNCs) of twin brothers. Whereas flow cytometric analysis failed to detect class II antigens on the cell surface of the patients' EBV-B cells and MNCs, examination of the genes coding for HLA-DR, -DQ, -DP, and the invariant chain (Ii) by reverse transcriptase-polymerase chain reaction amplification resulted in an unusual mRNA pattern in the B cell lines of the patients (HLA-DR alpha +, -DR beta, -DQ alpha +, -DQ beta -, -DP alpha -; -DP beta +, Ii+). In accordance with these findings no HLA-DR beta-specific protein was detected by immunoblotting, whereas low levels of HLA-DR alpha and normal levels of Ii were present. In contrast to EBV-B cells, the MNCs of both patients displayed a residual HLA-DR beta, -DQ beta, and -DP alpha mRNA signal. Furthermore, HLA-DR beta-specific protein was found in addition to HLA-DR alpha by immunoblotting of cell lysates, even though it was clearly decreased as compared with controls. Our results indicate that the defect in class II antigen expression is not necessarily present to the same extent in B cells and cells of other lineages. mRNA levels of HLA-DR beta were found to be enriched in adherent cells within the MNC fraction. Further investigations indicated that the MHC class II expressed is functional in antigen presentation, as the two boys' CD4+ T cells became activated and expressed interleukin-2R after stimulation of peripheral blood mononuclear cell cultures with recall antigen (tetanus toxoid). Furthermore, T cells tested in one of the two patients responded to both MHC class I and II allostimulation, and this response was inhibited by monoclonal antibodies of the respective specificity.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals Regulation of major histocompatibility complex gene expression in thyroid epithelial cells by methimazole and phenylmethimazole

2009 ◽  
Vol 204 (1) ◽  
pp. 57-66 ◽  
Author(s):  
Cesidio Giuliani ◽  
Ines Bucci ◽  
Valeria Montani ◽  
Dinah S Singer ◽  
Fabrizio Monaco ◽  
...  
Keyword(s):  
Gene Expression ◽  
Major Histocompatibility Complex ◽  
Epithelial Cells ◽  
Mhc Class I ◽  
Mhc Class Ii ◽  
Class Ii ◽  
Class I ◽  
Histocompatibility Complex ◽  
Ifn Γ ◽  
Mhc Class Ii Genes

Increased expression of major histocompatibility complex (MHC) class-I genes and aberrant expression of MHC class-II genes in thyroid epithelial cells (TECs) are associated with autoimmune thyroid diseases. Previous studies have shown that methimazole (MMI) reduces MHC class-I expression and inhibits interferon-γ (IFN-γ or IFNG as listed in the MGI Database)-induced expression of the MHC class-II genes in TECs. The action of MMI on the MHC class-I genes is transcriptional, but its mechanism has not been investigated previously. In the present study, we show that in Fisher rat thyroid cell line 5 cells, the ability of MMI and its novel derivative phenylmethimazole (C10) to decrease MHC class-I promoter activity is similar to TSH/cAMP suppression of MHC class-I and TSH receptor genes, and involves a 39 bp silencer containing a cAMP response element (CRE)-like site. Furthermore, we show that C10 decreases MHC class-I gene expression to a greater extent than MMI and at 10- to 50-fold lower concentrations. C10 also reduces the IFN-γ-induced increase in the expression of MHC class-I and MHC class-II genes more effectively than MMI. Finally, we show that in comparison to MMI, C10 is a better inhibitor of specific protein–DNA complexes that are formed with a CRE-like element on the MHC class-II promoter. These data support the conclusion that the immunosuppressive mechanism by which MMI and C10 inhibit MHC gene expression mimics ‘normal’ hormonal suppression by TSH/cAMP.

scholarly journals Discordance in the Epithelial Cell-Dendritic Cell Major Histocompatibility Complex Class II Immunoproteome: Implications for Chlamydia Vaccine Development

2019 ◽  
Vol 221 (5) ◽  
pp. 841-850
Author(s):  
Karuna P Karunakaran ◽  
Hong Yu ◽  
Xiaozhou Jiang ◽  
Queenie W T Chan ◽  
Leonard J Foster ◽  
...  
Keyword(s):  
T Cells ◽  
Major Histocompatibility Complex ◽  
Epithelial Cell ◽  
Epithelial Cells ◽  
Mhc Class Ii ◽  
Cd4 T Cells ◽  
Protective Immunity ◽  
Class Ii ◽  
Class I ◽  
Histocompatibility Complex

Abstract Background Chlamydia trachomatis and Chlamydia muridarum are intracellular bacterial pathogens of mucosal epithelial cells. CD4 T cells and major histocompatibility complex (MHC) class II molecules are essential for protective immunity against them. Antigens presented by dendritic cells (DCs) expand naive pathogen-specific T cells (inductive phase), whereas antigens presented by epithelial cells identify infected epithelial cells as targets during the effector phase. We previously showed that DCs infected by C trachomatis or C muridarum present epitopes from a limited spectrum of chlamydial proteins recognized by Chlamydia-specific CD4 T cells from immune mice. Methods We hypothesized that Chlamydia-infected DCs and epithelial cells present overlapping sets of Chlamydia-MHC class II epitopes to link inductive and effector phases to generate protective immunity. We tested that hypothesis by infecting an oviductal epithelial cell line with C muridarum, followed by immunoaffinity isolation and sequencing of MHC class I- and II-bound peptides. Results We identified 26 class I-bound and 4 class II-bound Chlamydia-derived peptides from infected epithelial cells. We were surprised to find that none of the epithelial cell class I- and class II-bound chlamydial peptides overlapped with peptides presented by DCs. Conclusions We suggest the discordance between the DC and epithelial cell immunoproteomes has implications for delayed clearance of Chlamydia and design of a Chlamydia vaccine.

scholarly journals Major histocompatibility complex-restricted recognition of retroviral superantigens by V beta 17+ T cells.

1992 ◽  
Vol 176 (1) ◽  
pp. 275-280 ◽  
Author(s):  
M A Blackman ◽  
F E Lund ◽  
S Surman ◽  
R B Corley ◽  
D L Woodland
Keyword(s):  
T Cells ◽  
Major Histocompatibility Complex ◽  
Mhc Class Ii ◽  
Class Ii ◽  
Major Histocompatibility ◽  
Direct Role ◽  
Histocompatibility Complex ◽  
Class Ii Mhc ◽  
Mhc Class Ii Molecules

It has been established that at least some V beta 17+ T cells interact with an endogenous superantigen encoded by the murine retrovirus, Mtv-9. To analyze the role of major histocompatibility complex (MHC) class II molecules in presenting the Mtv-9 encoded superantigen, vSAG-9 to V beta 17+ hybridomas, a panel of nine hybridomas was tested for their ability to respond to A20/2J (H-2d) and LBK (H-2a) cells which had been transfected with the vSAG-9 gene. Whereas some of the hybridomas recognized vSAG-9 exclusively in the context of H-2a, other hybridomas recognized vSAG-9 exclusively in the context of H-2d or in the context of both H-2d and H-2a. These results suggest that: (a) the class II MHC molecule plays a direct role in the recognition of retroviral superantigen by T cells, rather than serving simply as a platform for presentation; and, (b) it is likely that components of the TCR other than V beta are involved in the vSAG-9/TCR/class II interaction.

scholarly journals Specificity of Effector T Lymphocytes in Autologous Graft-Versus-Host Disease: Role of the Major Histocompatibility Complex Class II Invariant Chain Peptide

Blood ◽  
1997 ◽  
Vol 89 (6) ◽  
pp. 2203-2209 ◽  
Author(s):  
Allan D. Hess ◽  
Emilie C. Bright ◽  
Christopher Thoburn ◽  
Georgia B. Vogelsang ◽  
Richard J. Jones ◽  
...  
Keyword(s):  
T Cells ◽  
Major Histocompatibility Complex ◽  
T Lymphocytes ◽  
Mhc Class Ii ◽  
Class Ii ◽  
Effector T Cells ◽  
Invariant Chain ◽  
Target Cells ◽  
Graft Versus Host ◽  
Histocompatibility Complex

Abstract Administration of the immunosuppressive drug cyclosporine after autologous bone marrow transplantation induces a systemic autoimmune syndrome resembling graft-versus-host disease (GVHD). This syndrome termed autologous GVHD has significant antitumor activity. Associated with autologous GVHD is the development of T lymphocytes that recognize major histocompatibility complex (MHC) class II determinants, including self. The present studies attempted to characterize and define the molecular specificity of the effector T lymphocytes in autologous GVHD induced in patients with metastatic breast cancer. The results suggest that the effector cells associated with human autologous GVHD are CD8+ T lymphocytes expressing the α/β T-cell receptor. Additional studies show that the effector T cells recognize MHC class II antigens in association with a peptide from the invariant chain (CLIP). Pretreatment of autologous lymphoblast target cells with anti-CLIP antibody completely blocked lysis mediated by autologous GVHD effector T cells. On the other hand, force loading this peptide markedly enhanced the susceptibility of the target cells to recognition by the autoreactive T cells. The recognition of the MHC class II CLIP complex may account for the novel specificity of the effector T cells associated with human autologous GVHD. Moreover, identification of the target peptide may allow for the development of novel immunotherapeutic strategies to enhance the antitumor efficacy of autologous GVHD.

scholarly journals Reactivation of a major histocompatibility complex class II gene in mouse plasmacytoma cells and mouse T cells.

1992 ◽  
Vol 176 (5) ◽  
pp. 1465-1469 ◽  
Author(s):  
C H Chang ◽  
W L Fodor ◽  
R A Flavell
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
T Cell ◽  
B Cells ◽  
Mhc Class Ii ◽  
Class Ii ◽  
Histocompatibility Complex ◽  
Human T Cell ◽  
Human T Cell Line ◽  
Mhc Class Ii Genes

Terminally differentiated plasma cells and mouse T cells do not express major histocompatibility complex (MHC) class II genes although class II gene expression is observed in pre-B and mature B cells as well as in activated human T cells. Transient heterokaryons were prepared and analyzed to investigate the mechanisms of inactivation of MHC class II gene in mouse plasmacytoma cells and mouse T cells. The endogenous MHC class II genes in both mouse plasmacytoma cells and mouse T cells can be reactivated by factors present in B cells. This reactivation of class II gene is also observed by fusion with a human T cell line which expresses MHC class II genes, but not with a class II negative human T cell line. It appears that the loss of MHC class II gene expression during the terminal differentiation of B cells or T cell lineage is due to absence of positive regulatory factor(s) necessary for class II transcription.

scholarly journals Invariant chain and DM edit self-peptide presentation by major histocompatibility complex (MHC) class II molecules.

1996 ◽  
Vol 184 (5) ◽  
pp. 1747-1753 ◽  
Author(s):  
J F Katz ◽  
C Stebbins ◽  
E Appella ◽  
A J Sant
Keyword(s):  
T Cells ◽  
Major Histocompatibility Complex ◽  
Mhc Class Ii ◽  
Binding Pocket ◽  
Surface Expression ◽  
Class Ii ◽  
Invariant Chain ◽  
Generalized Function ◽  
Major Histocompatibility ◽  
Histocompatibility Complex

We have studied the consequences of invariant chain (Ii) and DM expression on major histocompatibility complex (MHC) class II function. Ii has a number of discrete functions in the biology of class II, including competitive blocking of peptide binding in the endoplasmic reticulum and enhancing localization in the endocytic compartments. DM is thought to act primarily in endosomes to promote dissociation of the Ii-derived (CLIP) peptide from the class II antigen-binding pocket and subsequent peptide loading. In this study, we have evaluated the functional role of Ii and DM by examining their impact on surface expression of epitopes recognized by a large panel of alloreactive T cells. We find most epitopes studied are influenced by both Ii and DM. Most strikingly, we find that surface expression of a significant fraction of peptide-class II complexes is extinguished, rather than enhanced, by DM expression within the APC. The epitopes antagonized by DM do not appear to be specific for CLIP. Finally, we found that DM was also able to extinguish recognition of a defined peptide derived from the internally synthesized H-2Ld protein. Thus, rather than primarily serving in the removal of CLIP, DM may have a more generalized function of editing the array of peptides that are presented by class II. This editing can be either positive or negative, suggesting that DM plays a specifying role in the display of peptides presented to CD4 T cells.

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