Monophosphoryl lipid A (MPL) upregulates major histocompatibility complex (MHC) class I expression by increasing interferon-gamma (IFN-γ)

ABSTRACT Recovery from leukemia induced by Friend virus complex (FV) requires strong CD4+ helper, CD8+ cytotoxic T-lymphocyte, and B-cell responses. The development of these immune responses is dependent on the major histocompatibility complex (MHC) (H-2) genotype of the mouse. InH-2b/b mice, which spontaneously recover from FV-induced erythroleukemia, neutralization of gamma interferon (IFN-γ) in vivo inhibited recovery, which indicated that IFN-γ was a necessary component of the immune response to FV. Furthermore, inH-2b/b mice, high numbers of IFN-γ-producing cells were detected after FV infection, whereas inH-2a/b mice, which have a low-recovery phenotype, only low numbers of IFN-γ-producing cells were detected. Similarly, H-2bm14/b mice, which cannot recover from FV infection due to a point mutation in one allele of theH-2Db gene, also had low numbers of IFN-γ-producing T cells. Surprisingly, this effect was observed for both CD8+ and CD4+ T cells. These findings reveal a novel influence of MHC class I genes on CD4+T-cell responses to viral infection. Furthermore, the influence of MHC class I genotype on the generation of both IFN-γ-producing CD4+ and CD8+ T cells helps explain the major impact of the H-2D gene on recovery from FV disease.

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Two Distinct Pathways Mediated by PA28 and hsp90 in Major Histocompatibility Complex Class I Antigen Processing

Journal of Experimental Medicine ◽

10.1084/jem.20011922 ◽

2002 ◽

Vol 196 (2) ◽

pp. 185-196 ◽

Cited By ~ 54

Author(s):

Taketoshi Yamano ◽

Shigeo Murata ◽

Naoki Shimbara ◽

Noriaki Tanaka ◽

Tomoki Chiba ◽

...

Keyword(s):

Major Histocompatibility Complex ◽

Mhc Class I ◽

Antigen Processing ◽

Class I ◽

Major Histocompatibility ◽

Wild Type ◽

Cell Type ◽

Histocompatibility Complex ◽

Ifn Γ ◽

Dependent Pathway

Major histocompatibility complex (MHC) class I ligands are mainly produced by the proteasome. Herein, we show that the processing of antigens is regulated by two distinct pathways, one requiring PA28 and the other hsp90. Both hsp90 and PA28 enhanced the antigen processing of ovalbumin (OVA). Geldanamycin, an inhibitor of hsp90, almost completely suppressed OVA antigen presentation in PA28α−/−/β−/− lipopolysaccharide blasts, but not in wild-type cells, indicating that hsp90 compensates for the loss of PA28 and is essential in the PA28-independent pathway. In contrast, treatment of cells with interferon (IFN)-γ, which induces PA28 expression, abrogated the requirement of hsp90, suggesting that IFN-γ enhances the PA28-dependent pathway, whereas it diminishes hsp90-dependent pathway. Importantly, IFN-γ did not induce MHC class I expressions in PA28-deficient cells, indicating a prominent role for PA28 in IFN-γ–stimulated peptide supply. Thus, these two pathways operate either redundantly or specifically, depending on antigen species and cell type.

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Degradation of Transcription Factor Rfx5 during the Inhibition of Both Constitutive and Interferon γ–Inducible Major Histocompatibility Complex Class I Expression in Chlamydia-Infected Cells

Journal of Experimental Medicine ◽

10.1084/jem.191.9.1525 ◽

2000 ◽

Vol 191 (9) ◽

pp. 1525-1534 ◽

Cited By ~ 149

Author(s):

Guangming Zhong ◽

Li Liu ◽

Tao Fan ◽

Peiyi Fan ◽

Hezhao Ji

Keyword(s):

Transcription Factor ◽

Major Histocompatibility Complex ◽

Mhc Class I ◽

Host Protein ◽

Class I ◽

Immune Recognition ◽

Major Histocompatibility ◽

Histocompatibility Complex ◽

Infected Cells ◽

Ifn Γ

We have previously shown that the obligate intracellular pathogen chlamydia can suppress interferon (IFN)-γ–inducible major histocompatibility complex (MHC) class II expression in infected cells by degrading upstream stimulation factor (USF)-1. We now report that chlamydia can also inhibit both constitutive and IFN-γ–inducible MHC class I expression in the infected cells. The inhibition of MHC class I molecule expression correlates well with degradation of RFX5, an essential downstream transcription factor required for both the constitutive and IFN-γ–inducible MHC class I expression. We further demonstrate that a lactacystin-sensitive proteasome-like activity identified in chlamydia-infected cell cytosolic fraction can degrade both USF-1 and RFX5. This proteasome-like activity is dependent on chlamydial but not host protein synthesis. Host preexisting proteasomes may not be required for the unique proteasome-like activity. These observations suggest that chlamydia-secreted factors may directly participate in the proteasome-like activity. Efforts to identify the chlamydial factors are underway. These findings provide novel information on the molecular mechanisms of chlamydial evasion of host immune recognition.

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Transcription of non-classic major histocompatibility complex (MHC) class I in the bovine placenta throughout gestation and after Brucella abortus infection

Veterinary Immunology and Immunopathology ◽

10.1016/j.vetimm.2015.06.014 ◽

2015 ◽

Vol 167 (3-4) ◽

pp. 166-170

Author(s):

Larissa Sarmento dos Santos ◽

Juliana Pinto da Silva Mol ◽

Auricélio Alves de Macedo ◽

Ana Patrícia Carvalho Silva ◽

Diego Luiz dos Santos Ribeiro ◽

...

Keyword(s):

Major Histocompatibility Complex ◽

Mhc Class I ◽

Brucella Abortus ◽

Class I ◽

Major Histocompatibility ◽

Bovine Placenta ◽

Histocompatibility Complex

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Major histocompatibility complex class I molecules mediate association of SV40 with caveolae.

Molecular Biology of the Cell ◽

10.1091/mbc.8.1.47 ◽

1997 ◽

Vol 8 (1) ◽

pp. 47-57 ◽

Cited By ~ 174

Author(s):

E Stang ◽

J Kartenbeck ◽

R G Parton

Keyword(s):

Major Histocompatibility Complex ◽

Mhc Class I ◽

Mammalian Cells ◽

Simian Virus 40 ◽

Class I ◽

Major Histocompatibility ◽

Surface Binding ◽

Histocompatibility Complex ◽

Mhc Class I Molecule ◽

Mhc Class I Molecules

Simian virus 40 (SV40) has been shown to enter mammalian cells via uncoated plasma membrane invaginations. Viral particles subsequently appear within the endoplasmic reticulum. In the present study, we have examined the surface binding and internalization of SV40 by immunoelectron microscopy. We show that SV40 associates with surface pits which have the characteristics of caveolae and are labeled with antibodies to the caveolar marker protein, caveolin-1. SV40 is believed to use major histocompatibility complex (MHC) class I molecules as cell surface receptors. Using a number of MHC class I-specific monoclonal antibodies, we found that both viral infection and association of virus with caveolae were strongly reduced by preincubation with anti-MHC class I antibodies. Because binding of SV40 to MHC class I molecules may induce clustering, we investigated whether antibody cross-linked class I molecules also redistributed to caveolae. Clusters of MHC class I molecules were indeed shown to be specifically associated with caveolin-labeled surface pits. Taken together, the results suggest that SV40 may make use of MHC class I molecule clustering and the caveolae pathway to enter mammalian cells.

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The expression of major histocompatibility complex (MHC) class I antigens in the brain differs markedly in acute and persistent infections with lymphocytic choriomeningitis virus (LCMV)

Journal of Neuroimmunology ◽

10.1016/0165-5728(92)90050-u ◽

1992 ◽

Vol 36 (2-3) ◽

pp. 193-198 ◽

Cited By ~ 31

Author(s):

L. Mucke ◽

M.B.A. Oldstone

Keyword(s):

Major Histocompatibility Complex ◽

Mhc Class I ◽

Lymphocytic Choriomeningitis ◽

Lymphocytic Choriomeningitis Virus ◽

Class I ◽

Major Histocompatibility ◽

Persistent Infections ◽

Histocompatibility Complex ◽

Mhc Class I Antigens ◽

The Brain

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Delayed rejection of major histocompatibility complex (MHC) class I and II incompatible skin grafts after Th2 vaccination

Immunology Letters ◽

10.1016/s0165-2478(97)85126-7 ◽

1997 ◽

Vol 56 ◽

pp. 33

Author(s):

A.L.J. Ogilvie ◽

T. Biedermann ◽

C.A. Sander ◽

P.I. Schiller ◽

M. Röcken

Keyword(s):

Major Histocompatibility Complex ◽

Mhc Class I ◽

Class I ◽

Skin Grafts ◽

Major Histocompatibility ◽

Histocompatibility Complex ◽

Delayed Rejection

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Nonimmune thyroid destruction results from transgenic overexpression of an allogeneic major histocompatibility complex class I protein

Molecular and Cellular Biology ◽

10.1128/mcb.13.3.1554-1564.1993 ◽

1993 ◽

Vol 13 (3) ◽

pp. 1554-1564

Author(s):

A G Frauman ◽

P Chu ◽

L C Harrison

Keyword(s):

Major Histocompatibility Complex ◽

Beta Cells ◽

Mhc Class I ◽

Pancreatic Beta Cells ◽

Class I ◽

General Mechanism ◽

Major Histocompatibility ◽

Cell Destruction ◽

Histocompatibility Complex ◽

Mhc Class I Molecules

The overexpression of major histocompatibility complex (MHC) class I molecules in endocrine epithelial cells is an early feature of autoimmune thyroid disease and insulin-dependent diabetes mellitus, which may reflect a cellular response, e.g., to viruses or toxins. Evidence from a transgenic model in pancreatic beta cells suggests that MHC class I overexpression could play an independent role in endocrine cell destruction. We demonstrate in this study that the transgenic overexpression of an allogeneic MHC class I protein (H-2Kb) linked to the rat thyroglobulin promoter, in H-2Kk mice homozygous for the transgene, leads to thyrocyte atrophy, hypothyroidism, growth retardation, and death. Thyrocyte atrophy occurred in the absence of lymphocytic infiltration. Tolerance to allogeneic class I was revealed by the reduced ability of primed lymphocytes from transgenic mice to lyse H-2Kb target cells in vitro. This nonimmune form of thyrocyte destruction and hypothyroidism recapitulates the beta-cell destruction and diabetes that results from transgenic overexpression of MHC class I molecules in pancreatic beta cells. Thus, we conclude that overexpression of MHC class I molecules may be a general mechanism that directly impairs endocrine epithelial cell viability.

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