Search results for "alpha-beta"
showing 10 items of 64 documents
Interleukin-36α axis is modulated in patients with primary Sjögren's syndrome.
2015
Summary The aim of this study was to investigate the expression of the interleukin (IL)-36 axis in patients with primary Sjögren's syndrome (pSS). Blood and minor labial salivary glands (MSG) biopsies were obtained from 35 pSS and 20 non-Sjögren's syndrome patients (nSS) patients. Serum IL-36α was assayed by enzyme-linked immunosorbent assay (ELISA). IL-36α, IL-36R, IL-36RA, IL-38, IL-22, IL-17, IL-23p19 and expression in MSGs was assessed by reverse transcription–polymerase chain reaction (RT–PCR), and tissue IL-36α and IL-38 expression was also investigated by immunohistochemistry (IHC). αβ and γδ T cells and CD68+ cells isolated from MSGs were also studied by flow cytometry and confocal …
MHC-restricted T cell receptor signaling is required for αβ TCR replacement of the pre T cell receptor
2008
A developmental block is imposed on CD25(+)CD44(-) thymocytes at the beta-selection checkpoint in the absence of the pre T cell receptor (preTCR) alpha-chain, pTalpha. Early surface expression of a transgenic alphabeta TCR has been shown to partially circumvent this block, such that thymocytes progress to the CD4(+)CD8(+) double-positive stage. We wanted to analyze whether a restricting MHC element is required for alphabeta TCR-expressing double-negative (DN) thymocytes to overcome the developmental block in pTalpha-deficient animals. We used the HY-I knock-in model that endows thymocytes with alphabeta TCR expression in the DN compartment but has the advantage of physiological expression l…
Human CD8 T lymphocytes recognize Mycobacterium tuberculosis antigens presented by HLA-E during active tuberculosis and express type 2 cytokines
2015
CD8 T cells contribute to protective immunity against Mycobacterium tuberculosis. In humans, M. tuberculosis reactive CD8 T cells typically recognize peptides associated to classical MHC class Ia molecules, but little information is available on CD8 T cells recognizing M. tuberculosis Ags presented by nonclassical MHC class Ib molecules. We show here that CD8 T cells from tuberculosis (TB) patients recognize HLA-E-binding M. tuberculosis peptides in a CD3/TCR αβ mediated and CD8-dependent manner, and represent an additional type of effector cells playing a role in immune response to M. tuberculosis during active infection. HLA-E-restricted recognition of M. tuberculosis peptides is detectab…
Improved assessment of T-cell receptor (TCR) VB repertoire in clinical specimens: combination of TCR-CDR3 spectratyping with flow cytometry-based TCR…
2002
ABSTRACTAntigen-specific T-cell responses may be described by combining three categories: (i) the specificity and effector functions of a T-cell population, (ii) the quantity of T-cell responses (i.e., the number of responding T cells within the CD4/CD8 population), and (iii) the “quality” of T cells (defined by the T-cell receptor [TCR] structure). Several methods to measure T-cell responses are now available including evaluation of T-cell precursors using limiting dilution, the enzyme-linked immunospot assay, ex vivo TCR variable (v)-segment analysis determined by flow cytometry, and TCR-CDR3 length analysis (spectratyping), as well as identification of peptide-specific T cells using majo…
A bicistronic vector backbone for rapid seamless cloning and chimerization of αβT-cell receptor sequences.
2020
To facilitate preclinical testing of T-cell receptors (TCRs) derived from tumor-reactive T-cell clones it is necessary to develop convenient and rapid cloning strategies for the generation of TCR expression constructs. Herein, we describe a pDONR™221 vector backbone allowing to generate Gateway™ compatible entry clones encoding optimized bicistronic αβTCR constructs. It harbors P2A-linked TCR constant regions and head-to-head-oriented recognition sites of the Type IIS restriction enzymes BsmBI and BsaI for seamless cloning of the TCRα and TCRβ V(D)J regions, respectively. Additional well-established TCR optimizations were incorporated to enhance TCR functionality. This included replacing of…
Cancer cell–autonomous contribution of type I interferon signaling to the efficacy of chemotherapy
2014
International audience; The immune system is routinely confronted with cell death resulting from the physiological turnover of renewable tissues, as well as from pathological insults of several types. We hypothesize the existence of a mechanism that allows the immune system to discriminate between physiological and pathological instances of cell death, but the factors that determine whether cellular demise is perceived as a neutral, tolerogenic or immunogenic event remain unclear 1. Infectious insults are accompanied by so-called microbe-associated molecular patterns (MAMPs), i.e., viral or bacterial products that activate immune cells through a panel of pattern-recognition receptors (PRRs)…
The Ability of Variant Peptides to Reverse the Nonresponsiveness of T Lymphocytes to the Wild-Type Sequence p53264–272 Epitope
2002
Abstract Recently, we observed that CTL specific for the wild-type (wt) sequence p53264–272 peptide could only be expanded ex vivo from PBMC of a subset of the HLA-A2.1+ normal donors or cancer patients tested. Surprisingly, the tumors of the responsive patients expressed normal levels of wt p53 and could be considered unlikely to present this epitope. In contrast, tumors of nonresponsive patients accumulated mutant p53 and were more likely to present this epitope. We sought to increase the responsive rate to the wt p53264–272 peptide of PBMC obtained from normal donors and patients by identifying more immunogenic variants of this peptide. Two such variants were generated by amino acid exch…
Human leucocyte antigen-A2 restricted and Mycobacterium tuberculosis 19-kDa antigen-specific CD8+ T-cell responses are oligoclonal and exhibit a T-ce…
2001
CD8+ T cells can be grouped into two different types of secretory T lymphocytes, based on the cytokine-secretion pattern upon antigen exposure: those with a T-cell cytotoxic type 1 response (Tc1), which secrete interferon-gamma (IFN-gamma), or those with a T-cell cytotoxic type 2 response, which secrete interleukin (IL)-4 and IL-10. We examined the CD8+ T-cell response directed against an immunodominant human leucocyte antigen (HLA)-A2-presented peptide derived from a 19-kDa Mycobacterium tuberculosis-associated antigen. T cells were examined by functional analysis and by T-cell receptor (TCR) complementarity-determining region 3 (CDR3)-spectratyping, which defines the complexity of a T-cel…
T Cell Receptor Mimic Peptidesand Their Potential Application in T-Cell-Mediated Diseas e
2001
<i>Background:</i> A T cell receptor (TCR) peptide was designed that mimics the intramembranous amino acid sequence of the TCR chain. Prior studies had shown that this mimic peptide would inhibit TCR signaling. This study was designed to investigate the use of this mimic peptide for the treatment of T-cell-mediated skin diseases. <i>Methods:</i> Synthesized mimic peptides were first tested for their T-cell-inhibitory effect in proliferation assays. Afterwards, mimic peptides were applied to murine ear skin prior to application of a contact allergen and tested for their inhibitory effect in the model of murine allergic contact sensitivity. The effect of epicutaneous t…
IL-23 receptor regulates unconventional IL-17-producing T cells that control bacterial infections.
2010
AbstractIL-23 plays an important role in autoimmune tissue inflammation and induces the generation of not fully characterized effector cells that mediate protection against pathogens. In this paper, we established the essential role of IL-23R in the host response against intracellular pathogens. IL-23 was critical for the expansion or maintenance of γδ and double negative (DN) αβ T cells. These cells were rapidly recruited to the site of infection and produced large amounts of IL-17, IFN-γ, and TNF-α. Notably, DN T cells transferred into L. monocytogenes-infected RAG2−/− mice prevented bacterial growth, confirming their protective role against intracellular pathogens. Our results show that …