scholarly journals Spontaneous internalization of Class I major histocompatibility complex molecules in T lymphoid cells.

1984 ◽  
Vol 159 (1) ◽  
pp. 193-207 ◽  
Author(s):  
D B Tse ◽  
B Pernis
Keyword(s):  
Mixed Lymphocyte Reaction ◽  
Lymphoid Cells ◽  
Class I ◽  
Con A ◽  
Class I Mhc ◽  
Complex Molecules ◽  
Mhc Molecules ◽  
Histocompatibility Complex ◽  
B Lymphoid

A low proportion of T lymphocytes in normal mouse spleen contains small intracytoplasmic vesicles showing Class I MHC molecules. After stimulation in vitro in a mixed lymphocyte reaction or by addition of Con A, the proportion of T cells with such intracytoplasmic vesicles increases progressively and becomes the majority. Labeling with fluorochrome-conjugated antibodies has shown that the vesicles are formed by internalization of molecules from the plasma membrane. The process is spontaneous and does not require cross-linking by antibodies or other ligands; it is selective inasmuch as other molecules (Thy-1 and T200 antigens) are not included and it is specific since it is not performed by other cells such as B lymphoid cells or fibroblasts. On the whole the process shows similarities with the internalization and recycling of other receptors, such as the receptors for different macromolecules of metabolic or informational significance, as seen in other cells. On the other hand, the specificity of Class I MHC mobilization in T lymphoid cells suggest a role for this process which is related to the immune function of these molecules.

scholarly journals HHV-7 U21 exploits Golgi quality control carriers to reroute class I MHC molecules to lysosomes

2020 ◽  
Vol 31 (3) ◽  
pp. 196-208
Author(s):  
Aaron T. Dirck ◽  
Melissa L. Whyte ◽  
Amy W. Hudson
Keyword(s):  
Quality Control ◽  
Major Histocompatibility Complex ◽  
Viral Protein ◽  
Class I ◽  
Major Histocompatibility ◽  
Class I Mhc ◽  
Complex Molecules ◽  
Mhc Molecules ◽  
Histocompatibility Complex

U21 is a viral protein that forms hetero-oligomers with class I major histocompatibility complex molecules and reroutes them to lysosomes. It is shown that U21 exits from the Golgi in a distinct clathrin-independent carrier that also carries unfolded and aggregated proteins to lysosomes.

scholarly journals Posttranscriptional Inhibition of Class I Major Histocompatibility Complex Presentation on Hepatocytes and Lymphoid Cells in Chronic Woodchuck Hepatitis Virus Infection

2000 ◽  
Vol 74 (10) ◽  
pp. 4483-4494 ◽  
Author(s):  
Tomasz I. Michalak ◽  
Paul D. Hodgson ◽  
Norma D. Churchill
Keyword(s):  
Chronic Hepatitis ◽  
Major Histocompatibility Complex ◽  
Hepatitis Virus ◽  
Lymphoid Cells ◽  
Class I ◽  
Woodchuck Hepatitis Virus ◽  
Class I Mhc ◽  
Mhc Molecules ◽  
Histocompatibility Complex ◽  
Hepatic Genes

ABSTRACT Woodchuck hepatitis virus (WHV), similar to human hepatitis B virus, causes acute liver inflammation that can progress to chronic hepatitis and hepatocellular carcinoma. WHV also invades cells of the host lymphatic system, where it persists for life. We report here that acute and chronic hepadnavirus hepatitis is characterized by a profound difference in the expression of class I major histocompatibility complex (MHC) molecules on the surface of infected hepatocytes and, notably, lymphoid cells. While acute WHV infection is accompanied by the enhanced hepatocyte surface presentation of class I MHC antigen and upregulated transcription of the relevant hepatic genes, inhibition of class I antigen display on liver cells is a uniform hallmark of chronic WHV infection. This inhibition in chronic hepatitis occurs despite augmented (as in acute infection) expression of hepatic genes for class I MHC heavy chain, β2-microglobulin, and transporters associated with antigen processing (TAP1 and TAP2). Further, the class I antigen inhibition is not related to the histological severity of hepatocellular injury, the extent of lymphocytic infiltrations, the level of intrahepatic gamma interferon induction, or the hepatic WHV load. Importantly, the antigen expression is also inhibited on organ lymphoid cells of chronically infected hosts. The results obtained in this study demonstrate that the defective presentation of class I MHC molecules on cells supporting persistent WHV replication is due to viral posttranscriptional interference. This event may diminish the susceptibility of infected hepatocytes to virus-specific T-cell-mediated elimination, hinder virus clearance, and deregulate the class I MHC-dependent functions of the host immune system. This multifarious effect could be critical for perpetuation of liver damage and evasion of the antiviral immunological surveillance in chronic infection and therefore could be supportive of hepadnavirus persistence.

scholarly journals Bovine papillomavirus type 1 oncoprotein E5 inhibits equine MHC class I and interacts with equine MHC I heavy chain

2009 ◽  
Vol 90 (12) ◽  
pp. 2865-2870 ◽  
Author(s):  
Barbara Marchetti ◽  
Elisabeth A. Gault ◽  
Marc S. Cortese ◽  
ZhengQiang Yuan ◽  
Shirley A. Ellis ◽  
...  
Keyword(s):  
Heavy Chain ◽  
Class I ◽  
Bovine Papillomavirus ◽  
Class I Mhc ◽  
Mhc I ◽  
Reading Frame ◽  
Histocompatibility Complex ◽  
Human Telomerase

Bovine papillomavirus type 1 is one of the aetiological agents of equine sarcoids. The viral major oncoprotein E5 is expressed in virtually all sarcoids, sarcoid cell lines and in vitro-transformed equine fibroblasts. To ascertain whether E5 behaves in equine cells as it does in bovine cells, we introduced the E5 open reading frame into fetal equine fibroblasts (EqPalF). As observed in primary bovine fibroblasts (BoPalF), E5 by itself could not immortalize EqPalF and an immortalizing gene, such as human telomerase (hTERT/hT), was required for the cells to survive selection. The EqPalF-hT-1E5 cells were morphologically transformed, elongated with many pseudopodia and capable of forming foci. Equine major histocompatibility complex class I (MHC I) was inhibited in these cells at least at two levels: transcription of MHC I heavy chain was inhibited and the MHC I complex was retained in the Golgi apparatus and prevented from reaching the cell surface. We conclude that, as in bovine cells and tumours, E5 is a player in the transformation of equine cells and the induction of sarcoids, and a potential major cause of MHC I downregulation and hence poor immune clearance of tumour cells.

scholarly journals Characterization of a Murine Cytomegalovirus Class I Major Histocompatibility Complex (MHC) Homolog: Comparison to MHC Molecules and to the Human Cytomegalovirus MHC Homolog

1998 ◽  
Vol 72 (1) ◽  
pp. 460-466 ◽  
Author(s):  
Tara L. Chapman ◽  
Pamela J. Bjorkman
Keyword(s):  
Major Histocompatibility Complex ◽  
Heavy Chain ◽  
Class I ◽  
Major Histocompatibility ◽  
Class I Mhc ◽  
Endogenous Peptides ◽  
Β2 Microglobulin ◽  
Mhc Molecules ◽  
Histocompatibility Complex ◽  
Infected Cells

ABSTRACT Both human and murine cytomegaloviruses (HCMV and MCMV) down-regulate expression of conventional class I major histocompatibility complex (MHC) molecules at the surfaces of infected cells. This allows the infected cells to evade recognition by cytotoxic T cells but leaves them susceptible to natural killer cells, which lyse cells that lack class I molecules. Both HCMV and MCMV encode class I MHC heavy-chain homologs that may function in immune response evasion. We previously showed that a soluble form of the HCMV class I homolog (UL18) expressed in Chinese hamster ovary cells binds the class I MHC light-chain β2-microglobulin and a mixture of endogenous peptides (M. L. Fahnestock, J. L. Johnson, R. M. R. Feldman, J. M. Neveu, W. S. Lane, and P. J. Bjorkman, Immunity 3:583–590, 1995). Consistent with this observation, sequence comparisons suggest that UL18 contains the well-characterized groove that serves as the binding site in MHC molecules for peptides derived from endogenous and foreign proteins. By contrast, the MCMV homolog (m144) contains a substantial deletion within the counterpart of its α2 domain and might not be expected to contain a groove capable of binding peptides. We have now expressed a soluble version of m144 and verified that it forms a heavy chain–β2-microglobulin complex. By contrast to UL18 and classical class I MHC molecules, m144 does not associate with endogenous peptides yet is thermally stable. These results suggest that UL18 and m144 differ structurally and might therefore serve different functions for their respective viruses.

scholarly journals Positive regulation of plasmacytoid dendritic cell function via Ly49Q recognition of class I MHC

2008 ◽  
Vol 205 (13) ◽  
pp. 3187-3199 ◽  
Author(s):  
Lee-Hwa Tai ◽  
Marie-Line Goulet ◽  
Simon Belanger ◽  
Noriko Toyama-Sorimachi ◽  
Nassima Fodil-Cornu ◽  
...  
Keyword(s):  
Immune Responses ◽  
Cell Function ◽  
Viral Infections ◽  
Plasmacytoid Dendritic Cell ◽  
Class I ◽  
Type I ◽  
Class I Mhc ◽  
Mhc Molecules

Plasmacytoid dendritic cells (pDCs) are an important source of type I interferon (IFN) during initial immune responses to viral infections. In mice, pDCs are uniquely characterized by high-level expression of Ly49Q, a C-type lectin-like receptor specific for class I major histocompatibility complex (MHC) molecules. Despite having a cytoplasmic immunoreceptor tyrosine-based inhibitory motif, Ly49Q was found to enhance pDC function in vitro, as pDC cytokine production in response to the Toll-like receptor (TLR) 9 agonist CpG-oligonucleotide (ODN) could be blocked using soluble monoclonal antibody (mAb) to Ly49Q or H-2Kb. Conversely, CpG-ODN–dependent IFN-α production by pDCs was greatly augmented upon receptor cross-linking using immobilized anti-Ly49Q mAb or recombinant H-2Kb ligand. Accordingly, Ly49Q-deficient pDCs displayed a severely reduced capacity to produce cytokines in response to TLR7 and TLR9 stimulation both in vitro and in vivo. Finally, TLR9-dependent antiviral responses were compromised in Ly49Q-null mice infected with mouse cytomegalovirus. Thus, class I MHC recognition by Ly49Q on pDCs is necessary for optimal activation of innate immune responses in vivo.

scholarly journals Ly-49 mediates EL4 lymphoma adhesion to isolated class I major histocompatibility complex molecules.

1994 ◽  
Vol 179 (3) ◽  
pp. 1011-1015 ◽  
Author(s):  
K P Kane
Keyword(s):  
Major Histocompatibility Complex ◽  
Gene Transfection ◽  
Negative Regulator ◽  
Class I ◽  
Major Histocompatibility ◽  
Cell Surface Molecule ◽  
Class I Mhc ◽  
Mhc Molecules ◽  
Histocompatibility Complex ◽  
T Lymphomas

Ly-49 is a recently identified cell surface molecule expressed on a subpopulation of natural killer (NK) cells and certain T lymphomas. It has been suggested, based on gene transfection and antibody blocking studies, that Ly-49 is a negative regulator of NK lytic activity, possibly through an interaction with target cell class I molecules. However, it has not been demonstrated that class I molecules indeed serve as ligands for Ly-49. We have found that T lymphomas expressing Ly-49 bind isolated class I major histocompatibility complex (MHC) molecules but not class II molecules immobilized on plastic. Adhesion to class I molecules was not found with T lymphomas lacking Ly-49 expression. The Ly-49 expressing EL4 lymphoma bound Dd, Dk, and Kb, but not Kd, Kk, or Db, thus demonstrating a restricted pattern of class I adhesion. The observed cell adhesion was class I density dependent, and binding to Dd and Dk was extensively inhibited by the A1 monoclonal antibody directed against Ly-49. These results provide direct evidence for Ly-49 serving as a receptor for a subset of class I MHC molecules.

scholarly journals In vitro maturation of immature thymocytes into immunocompetent T cells in the absence of direct thymic influence

1978 ◽  
Vol 148 (1) ◽  
pp. 32-45 ◽  
Author(s):  
C Irle ◽  
P-F Piguet ◽  
P Vassalli
Keyword(s):  
Lymph Node ◽  
Proliferative Response ◽  
Mixed Lymphocyte Reaction ◽  
Lymphoid Cells ◽  
Con A ◽  
Proliferating Cells ◽  
Surface Receptors ◽  
Helper Activity ◽  
Extracellular Factor

Peanut lectin (PNL) binds to a majority of mouse thymocytes (Thc) in suspension. By using cell affinity chromatography on a column of anti-PNL antibody, Thc populations at least 96 percent pure in PNL + or - cells, as judged by immunofluorescence, were obtained. PNL(+) cells are rich in Thy 1 and poor in H(2) antigens, cortisone sensitive, unresponsive to phytohemagglutinin (PHA), and immunologically incompetent, as judged by mixed lymphocyte reaction, popliteal lymph node graft-versus-host assay, and by testing helper activity in a primary in vitro antibody response to sheep erythrocytes; the converse is true of PNL(-) cells. Thus, PNL(+) and (-) cells appear to correspond to cortical and medullary Thc, respectively, as previously suggested. In culture, PNL(+) Thc show poor viability and a weak proliferative response to concanavalin A (Con A), except when supernate (SUP) of 24 h Con A stimulated lymph node lymphocyte cultures, or irradiated lymph node cells, are added, in which cases a strong proliferative response to the mitogen is observed. A variety of control experiments showed that the proliferating cells did not result from preferential stimulation of a few contaminating PNL(-) Thc present in the PNL(+) Thc cultures. The blasts resulting from PNL(+) Thc proliferation display mitogen-induced cytotoxicity, and give rise to a population of medium-sized lymphocytes, mostly PNL(-), poor in Thy 1 and rich in H(2) antigens, PHA responsive, and immunologically competent in the above-mentioned assays. Fresh PNL(+) Thc responded in mixed lymphocyte reaction in the presence of SUP (lectin depleted) and since incubation in SUP alone did not confer reactivity on PNL(+) Thc, it appears therefore that (a) immature Thc possess alloantigen and mitogen-specific surface receptors but lack the capacity to respond by proliferation to receptor triggering without the help of extracellular factor(s) released by mature lymphoid cells stimulated by mitogens (b) cell division is associated with the acquisition of immunological responsiveness, characteristic of mature T lymphocytes. The implications of these findings for the ontogenesis of thymus-derived lymphocytes, and for the possible traffic of Thc within and from the thymus, are discussed.

scholarly journals Suppression of Non-Random Fertilization by MHC Class I Antigens

2020 ◽  
Vol 21 (22) ◽  
pp. 8731
Author(s):  
Junki Kamiya ◽  
Woojin Kang ◽  
Keiichi Yoshida ◽  
Ryota Takagi ◽  
Seiya Kanai ◽  
...  
Keyword(s):  
Mhc Class I ◽  
Recognition System ◽  
Class I ◽  
Male Mice ◽  
Egg Recognition ◽  
Class I Mhc ◽  
Histocompatibility Complex ◽  
Self Recognition

Hermaphroditic invertebrates and plants have a self-recognition system on the cell surface of sperm and eggs, which prevents their self-fusion and enhances non-self-fusion, thereby contributing to genetic variation. However, the system of sperm–egg recognition in mammals is under debate. To address this issue, we explored the role of major histocompatibility complex class I (MHC class I, also known as histocompatibility 2-Kb or H2-Kb and H2-Db in mice) antigens by analyzing H2-Kb-/-H2-Db-/-β2-microglobulin (β2M)-/- triple-knockout (T-KO) male mice with full fertility. T-KO sperm exhibited an increased sperm number in the perivitelline space of wild-type (WT) eggs in vitro. Moreover, T-KO sperm showed multiple fusion with zona pellucida (ZP)-free WT eggs, implying that the ability of polyspermy block for sperm from T-KO males was weakened in WT eggs. When T-KO male mice were intercrossed with WT female mice, the percentage of females in progeny increased. We speculate that WT eggs prefer fusion with T-KO sperm, more specifically X-chromosome-bearing sperm (X sperm), suggesting the presence of preferential (non-random) fertilization in mammals, including humans.

scholarly journals Class I molecules retained in the endoplasmic reticulum bind antigenic peptides.

1993 ◽  
Vol 177 (6) ◽  
pp. 1633-1641 ◽  
Author(s):  
C K Lapham ◽  
I Bacík ◽  
J W Yewdell ◽  
K P Kane ◽  
J R Bennink
Keyword(s):  
Mhc Class I ◽  
Direct Evidence ◽  
Brefeldin A ◽  
Class I ◽  
Antigenic Peptides ◽  
Class I Mhc ◽  
Mhc Molecules ◽  
Histocompatibility Complex ◽  
Continuous Presence ◽  
Mhc Class I Molecules

We isolated major histocompatibility complex (MHC)-specific viral peptides from cells infected with influenza virus in the continuous presence of the drug brefeldin A, which blocks exocytosis of newly synthesized MHC class I molecules. MHC-specific peptides were also isolated from cells expressing mouse Kd class I MHC molecules whose cytoplasmic domain was substituted by that of the adenovirus E3/19K glycoprotein. This molecule was retained in an intracellular pre-Golgi complex compartment as demonstrated by immunocytochemical and biochemical means. Since we show that intracellular association of antigenic peptides with such retained class I molecules is necessary for their isolation from cellular extracts, this provides direct evidence that naturally processed peptides associate with class I MHC molecules in an early intracellular exocytic compartment.

Sign in / Sign up

Export Citation Format

Share Document