<i>In vivo</i> induction of H‐2K/D antigens by recombinant interferon‐γ

Momburg, Frank; Koch, Norbert; Möller, Peter; Moldenhauer, Gerhard; Hämmerling, Günter J.

doi:10.1002/eji.1830160516

Cited by 49 publications

(31 citation statements)

References 37 publications

(12 reference statements)

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“…In H-2k mice, loss of DM has an effect on E(k) but not A(k) class II molecules (37), supporting the notion that the need for the MHC class II chaperones is alleledependent. In vivo, Ii gene expression is not absolutely coordinated with MHC class II synthesis (38), and there are circumstances where deregulation of Ii may occur, for example during HIV infection, where Ii is a target of Nef (39). Our results therefore raise the possibility that expression levels of Ii could be exploited to manipulate the relative levels of stable MHC class II molecules, either by pathogens or for therapeutic benefit.…”

Section: Discussionmentioning

confidence: 87%

HLA-DP, HLA-DQ, and HLA-DR Have Different Requirements for Invariant Chain and HLA-DM

Lith

McEwen-Smith

Benham

2010

Journal of Biological Chemistry

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The MHC is central to the adaptive immune response. The human MHC class II is encoded by three different isotypes, HLA-DR, -DQ, and -DP, each being highly polymorphic. In contrast to HLA-DR, the intracellular assembly and trafficking of HLA-DP molecules have not been studied extensively. However, different HLA-DP variants can be either protective or risk factors for infectious diseases (e.g. hepatitis B), immune dysfunction (e.g. berylliosis), and autoimmunity (e.g. myasthenia gravis). Here, we establish a system to analyze the chaperone requirements for HLA-DP and to compare the assembly and trafficking of HLA-DP, -DQ, and -DR directly. Unlike HLA-DR1, HLA-DQ5 and HLA-DP4 can form SDS-stable dimers supported by invariant chain (Ii) in the absence of HLA-DM. Uniquely, HLA-DP also forms dimers in the presence of HLA-DM alone. In model antigen-presenting cells, SDS-stable HLA-DP complexes are resistant to treatments that prevent formation of SDS-stable HLA-DR complexes. The unexpected properties of HLA-DP molecules may help explain why they bind to a more restricted range of peptides than other human MHC class II proteins and frequently present viral peptides.

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Section: Discussionmentioning

confidence: 87%

HLA-DP, HLA-DQ, and HLA-DR Have Different Requirements for Invariant Chain and HLA-DM

Lith

McEwen-Smith

Benham

2010

Journal of Biological Chemistry

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“…Based on a large number of immunohistochemical studies in mice and humans, expression of MHC molecules on hepatocytes has been generally regarded as very low. 35,36 However, a recent report 11 has shown that these cells express abundant and conformationally stable MHC class I/peptide complexes with surface densities that are nearly as high as on splenocytes. Using quantitative flow cytometry techniques and calibration standards to adjust for the differences in cell size and autofluorescence between hepatocytes and splenocytes, it was demonstrated that, on a per cell basis, mouse hepatocytes express 7-to 16-fold higher levels of MHC class I molecules than splenocytes, whereas membrane densities were at least 30% to 75% as high as those estimated on splenic lymphocytes.…”

Section: Discussionmentioning

confidence: 99%

T lymphocytes interact with hepatocytes through fenestrations in murine liver sinusoidal endothelial cells

et al. 2006

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The liver has an established ability to induce tolerance. Recent evidence indicates that this unique property might be related to its distinctive architecture allowing T cells to be activated in situ independently of lymphoid tissues. Unlike lymph node-activated T cells, liver-activated T cells are shortlived, a mechanism that might contribute to the "liver tolerance effect." Although the potential role of hepatocytes as tolerogenic antigen-presenting cells has been demonstrated, the question as to whether these cells are able to interact with CD8 ؉ T cells in physiological settings remains controversial. Contradicting the immunological dogma stating that naïve T lymphocytes are prevented from interacting with parenchymal cells within non-lymphoid organs by an impenetrable endothelial barrier, we show here that the unique morphology of the liver sinusoidal endothelial cell (LSEC) permits interactions between lymphocytes and hepatocytes. Using electron microscopy, we demonstrate that liver resident lymphocytes as well as circulating naïve CD8 ؉ T cells make direct contact with hepatocytes through cytoplasmic extensions penetrating the endothelial fenestrations that perforate the LSECs. Furthermore, the expression of molecules required for primary T cell activation, MHC class I and ICAM-1, is polarized on hepatocytes to the perisinusoidal cell membrane, thus maximizing the opportunity for interactions with circulating lymphocytes. In conclusion, this study has identified, at the ultrastructural level, a unique type of interaction between naïve T lymphocytes and liver parenchymal cells in vivo. These results hold implications for the pathogenesis of viral hepatitis in which hepatocytes may represent the main antigen-presenting cell, and for the development of immune tolerance as lymphocytes pass through the liver.

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“…These alterations could be caused by mutation, recombination, or activation of normal MHC genes (8,9). Recent studies on human and mouse liver tissues indicated that neither class I nor class II MHC antigens were detectable on the surface of normal hepatocytes (10)(11)(12)(13)(14). On the other hand, it was discovered that hepatocytes of human patients with acute and chronic active hepatitis expressed MHC class I antigens (11)(12)(13), and that HBc antigen-containing hepatocytes may also express class II antigen (15).…”

Section: Introductionmentioning

confidence: 99%

Expression of class I and class II major histocompatibility antigens on human hepatocellular carcinoma.

Sung¹,

Hu²,

Hsu³

et al. 1989

J. Clin. Invest.

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Previous reports indicate that human hepatocytes do not express class I and class II MHC antigens. Our analyses on 10 human hepatocellular carcinoma (HCC) cell lines by immunofluorescence tests and RIA, demonstrate that all the human HCC cell lines tested express class I MHC antigens and among them, three poorly differentiated human HCC cell lines also express class II MHC antigens. Results of immunoprecipitation and/or Western blotting experiments indicate similarity in the chemical nature of both the class I and class II MHC antigens expressed by the human HCC cell lines and by a human B lymphoblastoid cell line Raji. Furthermore, a new variant form of class I antigen was detected in some of these HCC cell lines. Immunohistochemical studies of HCC tissues using the peroxidase-antiperoxidase staining method indicated that class I and class II antigens were detectable in 7 out of 11 and 3 out of 11 HCC tissues from patients, respectively. The availability of MHC class I antigen-positive cultured HCC cell lines, including the poorly differentiated lines that also express MHC class II antigen, has provided us with interesting models to study the relationship between expression of MHC antigen and transformation and differentiation of human hepatocytes. These studies will also allow us some insight into the role of MHC class I and class II antigen in the immunosensitivity and immunogenecity of HCC cells to the host-immune response.

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In vivo induction of H‐2K/D antigens by recombinant interferon‐γ

Cited by 49 publications

References 37 publications

HLA-DP, HLA-DQ, and HLA-DR Have Different Requirements for Invariant Chain and HLA-DM

HLA-DP, HLA-DQ, and HLA-DR Have Different Requirements for Invariant Chain and HLA-DM

T lymphocytes interact with hepatocytes through fenestrations in murine liver sinusoidal endothelial cells

Expression of class I and class II major histocompatibility antigens on human hepatocellular carcinoma.

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