Thymic epithelial cells: antigen presenting cells that regulate T cell repertoire and tolerance development

2012 ◽  
Vol 54 (1-3) ◽  
pp. 177-190 ◽  
Author(s):  
Konstantina Alexandropoulos ◽  
Nichole M. Danzl
Keyword(s):  
T Cell ◽  
Epithelial Cells ◽  
Antigen Presenting Cells ◽  
Thymic Epithelial Cells ◽  
T Cell Repertoire ◽  
Cell Repertoire ◽  
Tolerance Development ◽  
Antigen Presenting

scholarly journals The Aire family expands

2019 ◽  
Vol 216 (5) ◽  
pp. 1010-1011
Author(s):  
Adrian Liston ◽  
James Dooley
Keyword(s):  
T Cell ◽  
Epithelial Cells ◽  
Lymph Nodes ◽  
Thymic Epithelial Cells ◽  
T Cell Tolerance ◽  
T Cell Repertoire ◽  
Cell Tolerance ◽  
Cell Repertoire

T cell tolerance depends upon Aire-expressing cells to purge the T cell repertoire of autoreactive clones. Once thought to be the exclusive domain of thymic epithelial cells, a new study by Yamano et al. (https://doi.org/10.1084/jem.20181430) in this issue of JEM identifies ILC3-like cells in the lymph nodes with similar properties.

Shaping of the autoreactive T-cell repertoire by a splice variant of self protein expressed in thymic epithelial cells

10.1038/71540 ◽  
2000 ◽  
Vol 6 (1) ◽  
pp. 56-61 ◽  
Author(s):  
Ludger Klein ◽  
Matthias Klugmann ◽  
Klaus-Armin Nave ◽  
V K Tuohy ◽  
Bruno Kyewski
Keyword(s):  
T Cell ◽  
Epithelial Cells ◽  
Splice Variant ◽  
Thymic Epithelial Cells ◽  
T Cell Repertoire ◽  
Cell Repertoire ◽  
Autoreactive T Cell

scholarly journals Self-mediated positive selection of T cells sets an obstacle to the recognition of nonself

2021 ◽  
Vol 118 (37) ◽  
pp. e2100542118
Author(s):  
Balázs Koncz ◽  
Gergő M. Balogh ◽  
Benjamin T. Papp ◽  
Leó Asztalos ◽  
Lajos Kemény ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Epithelial Cells ◽  
Positive Selection ◽  
Thymic Epithelial Cells ◽  
Immune Recognition ◽  
T Cell Repertoire ◽  
Cell Repertoire ◽  
Adaptive Immune ◽  
Selection Of

Adaptive immune recognition is mediated by the binding of peptide–human leukocyte antigen complexes by T cells. Positive selection of T cells in the thymus is a fundamental step in the generation of a responding T cell repertoire: only those T cells survive that recognize human peptides presented on the surface of cortical thymic epithelial cells. We propose that while this step is essential for optimal immune function, the process results in a defective T cell repertoire because it is mediated by self-peptides. To test our hypothesis, we focused on amino acid motifs of peptides in contact with T cell receptors. We found that motifs rarely or not found in the human proteome are unlikely to be recognized by the immune system just like the ones that are not expressed in cortical thymic epithelial cells or not presented on their surface. Peptides carrying such motifs were especially dissimilar to human proteins. Importantly, we present our main findings on two independent T cell activation datasets and directly demonstrate the absence of naïve T cells in the repertoire of healthy individuals. We also show that T cell cross-reactivity is unable to compensate for the absence of positively selected T cells. Additionally, we show that the proposed mechanism could influence the risk for different infectious diseases. In sum, our results suggest a side effect of T cell positive selection, which could explain the nonresponsiveness to many nonself peptides and could improve the understanding of adaptive immune recognition.

scholarly journals NF‐κB‐inducing kinase contributes to normal development of cortical thymic epithelial cells: its possible role in shaping a proper T‐cell repertoire

Immunology ◽  
2020 ◽  
Vol 160 (2) ◽  
pp. 198-208
Author(s):  
Koji Eshima ◽  
Kana Misawa ◽  
Chihiro Ohashi ◽  
Haruka Noma ◽  
Kazuya Iwabuchi
Keyword(s):  
T Cell ◽  
Epithelial Cells ◽  
Normal Development ◽  
Thymic Epithelial Cells ◽  
T Cell Repertoire ◽  
Cell Repertoire

scholarly journals Expression of a Natural Tumor Antigen by Thymic Epithelial Cells Impairs the Tumor-Protective CD4+ T-Cell Repertoire

2005 ◽  
Vol 65 (14) ◽  
pp. 6443-6449 ◽  
Author(s):  
Rinke Bos ◽  
Suzanne van Duikeren ◽  
Thorbald van Hall ◽  
Patricia Kaaijk ◽  
Richard Taubert ◽  
...  
Keyword(s):  
T Cell ◽  
Epithelial Cells ◽  
Tumor Antigen ◽  
Cd4 T Cell ◽  
Thymic Epithelial Cells ◽  
T Cell Repertoire ◽  
Cell Repertoire

scholarly journals B7-CD28 co-stimulation modulates central tolerance via thymic clonal deletion and Treg generation through distinct mechanisms

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Masashi Watanabe ◽  
Ying Lu ◽  
Michael Breen ◽  
Richard J. Hodes
Keyword(s):  
Treg Cell ◽  
Specific Antigen ◽  
Cell Generation ◽  
Thymic Epithelial Cells ◽  
T Cell Repertoire ◽  
Cellular Mechanisms ◽  
Cell Repertoire ◽  
Clonal Deletion ◽  
Central Tolerance ◽  
Antigen Presenting

AbstractThe molecular and cellular mechanisms mediating thymic central tolerance and prevention of autoimmunity are not fully understood. Here we show that B7-CD28 co-stimulation and B7 expression by specific antigen-presenting cell (APC) types are required for clonal deletion and for regulatory T (Treg) cell generation from endogenous tissue-restricted antigen (TRA)-specific thymocytes. While B7-CD28 interaction is required for both clonal deletion and Treg induction, these two processes differ in their CD28 signaling requirements and in their dependence on B7-expressing dendritic cells, B cells, and thymic epithelial cells. Meanwhile, defective thymic clonal deletion due to altered B7-CD28 signaling results in the accumulation of mature, peripheral TRA-specific T cells capable of mediating destructive autoimmunity. Our findings thus reveal a function of B7-CD28 co-stimulation in shaping the T cell repertoire and limiting autoimmunity through both thymic clonal deletion and Treg cell generation.

scholarly journals Atypical TRAV1-2− T cell receptor recognition of the antigen-presenting molecule MR1

2020 ◽  
Vol 295 (42) ◽  
pp. 14445-14457 ◽  
Author(s):  
Wael Awad ◽  
Erin W. Meermeier ◽  
Maria L. Sandoval-Romero ◽  
Jérôme Le Nours ◽  
Aneta H. Worley ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
T Cell Repertoire ◽  
Cell Repertoire ◽  
Mait Cells ◽  
Receptor Recognition ◽  
Antigen Presenting ◽  
Β Chain ◽  
Complementarity Determining Region

MR1 presents vitamin B–related metabolites to mucosal associated invariant T (MAIT) cells, which are characterized, in part, by the TRAV1-2+ αβ T cell receptor (TCR). In addition, a more diverse TRAV1-2− MR1-restricted T cell repertoire exists that can possess altered specificity for MR1 antigens. However, the molecular basis of how such TRAV1-2− TCRs interact with MR1–antigen complexes remains unclear. Here, we describe how a TRAV12-2+ TCR (termed D462-E4) recognizes an MR1–antigen complex. We report the crystal structures of the unliganded D462-E4 TCR and its complex with MR1 presenting the riboflavin-based antigen 5-OP-RU. Here, the TRBV29-1 β-chain of the D462-E4 TCR binds over the F′-pocket of MR1, whereby the complementarity-determining region (CDR) 3β loop surrounded and projected into the F′-pocket. Nevertheless, the CDR3β loop anchored proximal to the MR1 A′-pocket and mediated direct contact with the 5-OP-RU antigen. The D462-E4 TCR footprint on MR1 contrasted that of the TRAV1-2+ and TRAV36+ TCRs' docking topologies on MR1. Accordingly, diverse MR1-restricted T cell repertoire reveals differential docking modalities on MR1, thus providing greater scope for differing antigen specificities.

scholarly journals High Level Expression of MHC-II in HPV+ Head and Neck Cancers Suggests that Tumor Epithelial Cells Serve an Important Role as Accessory Antigen Presenting Cells

Cancers ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1129 ◽  
Author(s):  
Steven F. Gameiro ◽  
Farhad Ghasemi ◽  
John W. Barrett ◽  
Anthony C. Nichols ◽  
Joe S. Mymryk
Keyword(s):  
T Cell ◽  
Epithelial Cells ◽  
Antigen Presentation ◽  
Head And Neck ◽  
Antigen Presenting Cells ◽  
Human Papillomaviruses ◽  
Mhc Ii ◽  
Hpv Status ◽  
Antigen Presenting ◽  
The Impact

High-risk human papillomaviruses (HPVs) are responsible for a subset of head and neck squamous cell carcinomas (HNSCC). Expression of class II major histocompatibility complex (MHC-II) is associated with antigen presenting cells (APCs). During inflammation, epithelial cells can be induced to express MHC-II and function as accessory APCs. Utilizing RNA-seq data from over 500 HNSCC patients from The Cancer Genome Atlas, we determined the impact of HPV-status on the expression of MHC-II genes and related genes involved in their regulation, antigen presentation, and T-cell co-stimulation. Expression of virtually all MHC-II genes was significantly upregulated in HPV+ carcinomas compared to HPV− or normal control tissue. Similarly, genes that encode products involved in antigen presentation were also significantly upregulated in the HPV+ cohort. In addition, the expression of CIITA and RFX5—regulators of MHC-II—were significantly upregulated in HPV+ tumors. This coordinated upregulation of MHC-II genes was correlated with higher intratumoral levels of interferon-gamma in HPV+ carcinomas. Furthermore, genes that encode various co-stimulatory molecules involved in T-cell activation and survival were also significantly upregulated in HPV+ tumors. Collectively, these results suggest a previously unappreciated role for epithelial cells in antigen presentation that functionally contributes to the highly immunogenic tumor microenvironment observed in HPV+ HNSCC.

scholarly journals CD1b tetramers bind αβ T cell receptors to identify a mycobacterial glycolipid-reactive T cell repertoire in humans

2011 ◽  
Vol 208 (9) ◽  
pp. 1741-1747 ◽  
Author(s):  
Anne G. Kasmar ◽  
Ildiko van Rhijn ◽  
Tan-Yun Cheng ◽  
Marie Turner ◽  
Chetan Seshadri ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptors ◽  
Direct Detection ◽  
Ex Vivo ◽  
T Cell Repertoire ◽  
Cell Repertoire ◽  
Cell Receptors ◽  
Cell Staining ◽  
Antigen Presenting

Microbial lipids activate T cells by binding directly to CD1 and T cell receptors (TCRs) or by indirect effects on antigen-presenting cells involving induction of lipid autoantigens, CD1 transcription, or cytokine release. To distinguish among direct and indirect mechanisms, we developed fluorescent human CD1b tetramers and measured T cell staining. CD1b tetramer staining of T cells requires glucose monomycolate (GMM) antigens, is specific for TCR structure, and is blocked by a recombinant clonotypic TCR comprised of TRAV17 and TRBV4-1, proving that CD1b–glycolipid complexes bind the TCR. GMM-loaded tetramers brightly stain a small subpopulation of blood-derived cells from humans infected with Mycobacterium tuberculosis, providing direct detection of a CD1b-reactive T cell repertoire. Polyclonal T cells from patients sorted with tetramers are activated by GMM antigens presented by CD1b. Whereas prior studies emphasized CD8+ and CD4−CD8− CD1b-restricted clones, CD1b tetramer-based studies show that nearly all cells express the CD4 co-receptor. These findings prove a cognate mechanism whereby CD1b–glycolipid complexes bind to TCRs. CD1b tetramers detect a natural CD1b-restricted T cell repertoire ex vivo with unexpected features, opening a new investigative path to study the human CD1 system.

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