Differential expression of CLIP: MHC class II and conventional endogenous peptide: MHC class II complexes by thymic epithelial cells and peripheral antigen-presenting cells

1996 ◽  
Vol 26 (12) ◽  
pp. 3185-3193 ◽  
Author(s):  
Andrew Farr ◽  
Paul C. Deroos ◽  
Susan Eastman ◽  
Alexander Y. Rudensky
Keyword(s):  
Epithelial Cells ◽  
Differential Expression ◽  
Mhc Class Ii ◽  
Antigen Presenting Cells ◽  
Class Ii ◽  
Thymic Epithelial Cells ◽  
Endogenous Peptide ◽  
Antigen Presenting

scholarly journals Quantitative Analysis of the Efficiency of Clonal Deletion in the Thymus

1994 ◽  
Vol 4 (1) ◽  
pp. 43-53 ◽  
Author(s):  
Lisa M. Spain ◽  
Leslie J. Berg
Keyword(s):  
Epithelial Cells ◽  
Mhc Class Ii ◽  
Negative Selection ◽  
Gene Dosage ◽  
Antigen Presenting Cells ◽  
Class Ii ◽  
Clonal Deletion ◽  
Self Tolerance ◽  
Antigen Presenting ◽  
Mhc Class Ii Molecules

One of the major mechanisms for establishing self-tolerance is the clonal deletion of self-reactive T cells during their development in the thymus. Using a TCR transgenic mouse model, we have established a quantitativeex vivoassay for examining the sensitivity and specificity of negative selection. Thymic organ cultures established from mice of varying MHC haplotypes were incubated with antigen, and the efficiency of clonal deletion assessed. We show here that clonal deletion of CD4+8+thymocytes is sensitive to both the gene dosage and the allelic variation of MHC class II molecules expressed on thymic antigen-presenting cells. We also find that when epithelial cells in the thymic cortex are the only antigen-presenting cells expressing the appropriate MHC class II molecules, negative selection of CD4+8+cells is as efficient as when antigen is presented on all thymic antigen-presenting cells. These studies demonstrate that the induction of self-tolerance via clonal deletion in the thymus is a function not only of antigen concentration, but also of MHC class II cell-surface density. In addition, together with the reports of others, these results confirm that cortical epithelial cells can mediate negative selection, and demonstrate that they do so in the intact thymic microenvironment.

scholarly journals Selective Abrogation of Major Histocompatibility Complex Class II Expression on Extrahematopoietic Cells in Mice Lacking Promoter IV of the Class II Transactivator Gene

2001 ◽  
Vol 194 (4) ◽  
pp. 393-406 ◽  
Author(s):  
Jean-Marc Waldburger ◽  
Tobias Suter ◽  
Adriano Fontana ◽  
Hans Acha-Orbea ◽  
Walter Reith
Keyword(s):  
Mhc Class Ii ◽  
Antigen Presenting Cells ◽  
Class Ii ◽  
Thymic Epithelial Cells ◽  
Class Ii Transactivator ◽  
Ifn Γ ◽  
Definition Of ◽  
Antigen Presenting ◽  
Mhcii Expression

MHC class II (MHCII) molecules play a pivotal role in the induction and regulation of immune responses. The transcriptional coactivator class II transactivator (CIITA) controls MHCII expression. The CIITA gene is regulated by three independent promoters (pI, pIII, pIV). We have generated pIV knockout mice. These mice exhibit selective abrogation of interferon (IFN)-γ–induced MHCII expression on a wide variety of non-bone marrow–derived cells, including endothelia, epithelia, astrocytes, and fibroblasts. Constitutive MHCII expression on cortical thymic epithelial cells, and thus positive selection of CD4+ T cells, is also abolished. In contrast, constitutive and inducible MHCII expression is unaffected on professional antigen-presenting cells, including B cells, dendritic cells, and IFN-γ–activated cells of the macrophage lineage. pIV−/− mice have thus allowed precise definition of CIITA pIV usage in vivo. Moreover, they represent a unique animal model for studying the significance and contribution of MHCII-mediated antigen presentation by nonprofessional antigen-presenting cells in health and disease.

Allotransplantation of culture-isolated neonatal rat islet tissue. Absence of MHC class II positive antigen-presenting cells in nonimmunogenic islets

Diabetes ◽  
1989 ◽  
Vol 38 (2) ◽  
pp. 146-151 ◽  
Author(s):  
O. D. Hegre ◽  
R. J. Ketchum ◽  
H. Popiela ◽  
C. R. Eide ◽  
R. M. Meloche ◽  
...  
Keyword(s):  
Mhc Class Ii ◽  
Antigen Presenting Cells ◽  
Class Ii ◽  
Neonatal Rat ◽  
Islet Tissue ◽  
Antigen Presenting

scholarly journals Stratification of Antigen-presenting Cells within the Normal Cornea

2009 ◽  
Vol 1 ◽  
pp. OED.S2813 ◽  
Author(s):  
Jared E. Knickelbein ◽  
Simon C. Watkins ◽  
Paul G. Mcmenamin ◽  
Robert L. Hendricks
Keyword(s):  
Bone Marrow ◽  
Basement Membrane ◽  
Mhc Class Ii ◽  
Fluorescent Protein ◽  
Antigen Presenting Cells ◽  
Class Ii ◽  
Apical Surface ◽  
Bone Marrow Derived Cells ◽  
Green Fluorescent ◽  
Antigen Presenting

The composition and location of professional antigen presenting cells (APC) varies in different mucosal surfaces. The cornea, long considered an immune-privileged tissue devoid of APCs, is now known to host a heterogeneous network of bone marrow-derived cells. Here, we utilized transgenic mice that express enhanced green fluorescent protein (EGFP) from the CD 11c promoter (pCD11c) in conjunction with immunohistochemical staining to demonstrate an interesting stratification of APCs within non-inflamed murine corneas. pCD11c+ dendritic cells (DCs) reside in the basal epithelium, seemingly embedded in the basement membrane. Most DCs express MHC class II on at least some dendrites, which extend up to 50 μm in length and traverse up 20 μm tangentially towards the apical surface of the epithelium. The DC density diminishes from peripheral to central cornea. Beneath the DCs and adjacent to the stromal side of the basement membrane reside pCD11c–CD11b+ putative macrophages that express low levels of MHC class II. Finally, MHC class II–pCD11c–CD11b+ cells form a network throughout the remainder of the stroma. This highly reproducible stratification of bone marrow-derived cells is suggestive of a progression from an APC function at the exposed corneal surface to an innate immune barrier function deeper in the stroma.

Endocytosis and Biosynthetic Transport of Murine MHC Class II Molecules in Antigen Presenting Cells

Endocytosis ◽  
1992 ◽  
pp. 341-342
Author(s):  
J. Davoust ◽  
P. Cosson ◽  
J. M. Escola ◽  
J. Henry ◽  
M. Humbert ◽  
...  
Keyword(s):  
Mhc Class Ii ◽  
Antigen Presenting Cells ◽  
Class Ii ◽  
Antigen Presenting ◽  
Mhc Class Ii Molecules

Allotransplantation of Culture-Isolated Neonatal Rat Islet Tissue: Absence of MHC Class II Positive Antigen-Presenting Cells in Nonimmunogenic Islets

Diabetes ◽  
1989 ◽  
Vol 38 (2) ◽  
pp. 146-151 ◽  
Author(s):  
O. D. Hegre ◽  
R. J. Ketchum ◽  
H. Popiela ◽  
C. R. Eide ◽  
R. M. Meloche ◽  
...  
Keyword(s):  
Mhc Class Ii ◽  
Antigen Presenting Cells ◽  
Class Ii ◽  
Neonatal Rat ◽  
Islet Tissue ◽  
Antigen Presenting

scholarly journals Macroautophagy substrates are loaded onto MHC class II of medullary thymic epithelial cells for central tolerance

2013 ◽  
Vol 210 (2) ◽  
pp. 287-300 ◽  
Author(s):  
Martin Aichinger ◽  
Chunyan Wu ◽  
Jelena Nedjic ◽  
Ludger Klein
Keyword(s):  
Epithelial Cells ◽  
Mhc Class Ii ◽  
Negative Selection ◽  
Class Ii ◽  
Single Amino Acid ◽  
Thymic Epithelial Cells ◽  
Clonal Deletion ◽  
Central Tolerance ◽  
Metabolic Functions ◽  
Physiological Relevance

Macroautophagy serves cellular housekeeping and metabolic functions through delivery of cytoplasmic constituents for lysosomal degradation. In addition, it may mediate the unconventional presentation of intracellular antigens to CD4+ T cells; however, the physiological relevance of this endogenous MHC class II loading pathway remains poorly defined. Here, we characterize the role of macroautophagy in thymic epithelial cells (TECs) for negative selection. Direct presentation for clonal deletion of MHC class II–restricted thymocytes required macroautophagy for a mitochondrial version of a neo-antigen, but was autophagy-independent for a membrane-bound form. A model antigen specifically expressed in Aire+ medullary TECs (mTECs) induced efficient deletion via direct presentation when targeted to autophagosomes, whereas interference with autophagosomal routing of this antigen through exchange of a single amino acid or ablation of an essential autophagy gene abolished direct presentation for negative selection. Furthermore, when this autophagy substrate was expressed by mTECs in high amounts, endogenous presentation and indirect presentation by DCs operated in a redundant manner, whereas macroautophagy-dependent endogenous loading was essential for clonal deletion at limiting antigen doses. Our findings suggest that macroautophagy supports central CD4+ T cell tolerance through facilitating the direct presentation of endogenous self-antigens by mTECs.

Expression of intercellular adhesion molecule 1 (ICAM-1) on the human oviductal epithelium and mediation of lymphoid cell adherence

Reproduction ◽  
2000 ◽  
pp. 115-123 ◽  
Author(s):  
E Utreras ◽  
P Ossandon ◽  
C Acuna-Castillo ◽  
L Varela-Nallar ◽  
C Muller ◽  
...  
Keyword(s):  
Mhc Class Ii ◽  
Adhesion Molecule ◽  
Antigen Presenting Cells ◽  
Class Ii ◽  
Intercellular Adhesion ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1 ◽  
Oviductal Epithelium ◽  
Antigen Presenting ◽  
Human Oviduct

The epithelium of the human oviduct expresses the major histocompatibility complex (MHC) class II and shows endocytic properties towards luminal antigens. Therefore, the epithelial cells might behave as antigen-presenting cells, inducing a local immune response. The activation of antigen-specific T cells not only requires presentation of the peptide antigen by MHC class II, but also the presence of co-stimulatory molecules in the antigen-presenting cells. Therefore, the expression of the intercellular adhesion molecule 1 (ICAM-1) was examined in the epithelium of the human oviduct. Most oviducts showed epithelial ICAM-1 expression, as assessed by immunocytochemistry, western blot analysis and RT-PCR assay, and the expression was restricted to the luminal border of ciliated and secretory cells. Interferon gamma, interleukin 1 and lipopolysaccharide treatments increased the percentage of ICAM-1-positive cells in primary cultures, indicating that the expression of ICAM-1 in the oviduct might be upregulated in vivo by inflammatory cytokines or bacterial infections. Binding assays between allogenic phytohaemagglutinin-activated lymphocytes and epithelial monolayers expressing ICAM-1 demonstrated that this molecule stimulated lymphocyte adherence. The presence of ICAM-1, in addition to MHC class II, supports the putative role of the oviductal epithelium in antigen presentation. The exclusive apical distribution of ICAM-1 indicates that T-cell activation would occur in a polarized manner. Binding of lymphoid cells to the surface of the oviductal epithelium may help to retain these immune cells that are required for the clearance of pathogens.

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