scholarly journals Human Major Histocompatibility Complex (MHC) Class I Molecules with Disulfide Traps Secure Disease-related Antigenic Peptides and Exclude Competitor Peptides

2008 ◽  
Vol 283 (12) ◽  
pp. 7480-7490 ◽  
Author(s):  
Steven M. Truscott ◽  
Xiaoli Wang ◽  
Lonnie Lybarger ◽  
William E. Biddison ◽  
Cortez McBerry ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
Mhc Class I ◽  
Class I ◽  
Antigenic Peptides ◽  
Major Histocompatibility ◽  
Human Major Histocompatibility Complex ◽  
Histocompatibility Complex ◽  
Mhc Class I Molecules

scholarly journals Tumorigenicity conferred to lymphoma mutant by major histocompatibility complex-encoded transporter gene.

1993 ◽  
Vol 177 (1) ◽  
pp. 201-205 ◽  
Author(s):  
L Franksson ◽  
E George ◽  
S Powis ◽  
G Butcher ◽  
J Howard ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
Nk Cells ◽  
Mhc Class I ◽  
Nk Cell ◽  
Class I ◽  
Antigenic Peptides ◽  
Major Histocompatibility ◽  
Histocompatibility Complex ◽  
Mhc Class I Molecules

Presentation of antigenic peptides by major histocompatibility complex (MHC) class I molecules requires MHC-encoded molecules of the adenosine triphosphate binding cassette (ABC) family. Defects in these proteins represent a potential risk, since they are essential links in the machinery of T cell-mediated surveillance which continuously scrutinizes peptide samples of cellular proteins. Nevertheless, transfection of the mouse lymphoma mutant RMA-S with the rat ABC gene mtp2a (homologue to mouse HAM2 and human RING11), commonly termed TAP-2 genes, led to a marked increase in tumor outgrowth potential in vivo. This occurred despite restored antigen presentation and sensitivity to cytotoxic T lymphocytes, and was found to be due to escape from natural killer (NK) cell-mediated rejection. It has previously been proposed that adequate expression of self-MHC class I is one important mechanism to avoid elimination by NK cells. Our data argue that a defect in the machinery responsible for processing and loading of peptides into MHC class I molecules is sufficient to render cells sensitive to elimination by NK cells. The latter thus appear to function as a surveillance of the peptide surveillance machinery.

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

1997 ◽  
Vol 8 (1) ◽  
pp. 47-57 ◽  
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.

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

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.

scholarly journals Porcine major histocompatibility complex (MHC) class I molecules and analysis of their peptide-binding specificities

2011 ◽  
Vol 63 (12) ◽  
pp. 821-834 ◽  
Author(s):  
Lasse Eggers Pedersen ◽  
Mikkel Harndahl ◽  
Michael Rasmussen ◽  
Kasper Lamberth ◽  
William T. Golde ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
Mhc Class I ◽  
Peptide Binding ◽  
Class I ◽  
Major Histocompatibility ◽  
Histocompatibility Complex ◽  
Mhc Class I Molecules

scholarly journals A Common Inhibitory Receptor for Major Histocompatibility Complex Class I Molecules on Human Lymphoid and Myelomonocytic Cells

1997 ◽  
Vol 186 (11) ◽  
pp. 1809-1818 ◽  
Author(s):  
Marco Colonna ◽  
Francisco Navarro ◽  
Teresa Bellón ◽  
Manuel Llano ◽  
Pilar García ◽  
...  
Keyword(s):  
T Cells ◽  
Major Histocompatibility Complex ◽  
B Cells ◽  
Mhc Class I ◽  
Killer Cell ◽  
Class I ◽  
Major Histocompatibility ◽  
Histocompatibility Complex ◽  
Myelomonocytic Cells ◽  
Mhc Class I Molecules

Natural killer (NK) cell–mediated lysis is negatively regulated by killer cell inhibitory receptors specific for major histocompatibility complex (MHC) class I molecules. In this study, we characterize a novel inhibitory MHC class I receptor of the immunoglobulin-superfamily, expressed not only by subsets of NK and T cells, but also by B cells, monocytes, macrophages, and dendritic cells. This receptor, called Ig-like transcript (ILT)2, binds MHC class I molecules and delivers a negative signal that inhibits killing by NK and T cells, as well as Ca2+ mobilization in B cells and myelomonocytic cells triggered through the B cell antigen receptor and human histocompatibility leukocyte antigens (HLA)–DR, respectively. In addition, myelomonocytic cells express receptors homologous to ILT2, which are characterized by extensive polymorphism and might recognize distinct HLA class I molecules. These results suggest that diverse leukocyte lineages have adopted recognition of self–MHC class I molecules as a common strategy to control cellular activation during an immune response.

scholarly journals E3/19K from adenovirus 2 is an immunosubversive protein that binds to a structural motif regulating the intracellular transport of major histocompatibility complex class I proteins.

1990 ◽  
Vol 172 (6) ◽  
pp. 1653-1664 ◽  
Author(s):  
W A Jefferies ◽  
H G Burgert
Keyword(s):  
Major Histocompatibility Complex ◽  
Cell Surface ◽  
Mhc Class I ◽  
Intracellular Transport ◽  
Surface Expression ◽  
Class I ◽  
Cell Surface Expression ◽  
Major Histocompatibility ◽  
Histocompatibility Complex ◽  
Mhc Class I Molecules

We have previously expressed in transgenic mice a chimeric H-2Kd/Kk protein called C31, which contains the extracellular alpha 1 domain of Kd, whereas the rest of the molecule is of Kk origin. This molecule functions as a restriction element for alloreactive and influenza A-specific cytotoxic T lymphocytes (CTL) but is only weakly expressed at the cell surface of splenocytes. Here, we show that the low cell surface expression is the result of slow intracellular transport and processing of the C31 protein. A set of hybrid molecules between Kd and Kk were used to localize the regions in major histocompatibility complex (MHC) molecules that are important for their intracellular transport and to further localize the structures responsible for binding to the adenovirus 2 E3/19K protein. This protein appears to be an important mediator of adenovirus persistence. It acts by binding to the immaturely glycosylated forms of MHC class I proteins in the endoplasmic reticulum (ER), preventing their passage to the cell surface and thereby reducing the recognition of infected cells by virus-specific T cells. We find the surprising result that intracellular transport and E3/19K binding are controlled primarily by the first half of the second domain of Kd, thus localizing these phenomena to the five polymorphic residues in this region of the Kd protein. This result implies that the E3/19K protein may act by inhibiting peptide binding or by disrupting the oligomerization of MHC class I molecules required for transport out of the ER. Alternatively, the E3/19K protein may inhibit the function of a positively acting transport molecule necessary for cell surface expression of MHC class I molecules.

scholarly journals Selection and Expansion of CD8α/α1 T Cell Receptor α/β1 Intestinal Intraepithelial Lymphocytes in the Absence of Both Classical Major Histocompatibility Complex Class I and Nonclassical Cd1 Molecules

1999 ◽  
Vol 190 (6) ◽  
pp. 885-890 ◽  
Author(s):  
Se-Ho Park ◽  
Delphine Guy-Grand ◽  
François A. Lemonnier ◽  
Chyung-Ru Wang ◽  
Albert Bendelac ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
Mhc Class I ◽  
Antigen Processing ◽  
Intraepithelial Lymphocytes ◽  
Class I ◽  
Major Histocompatibility ◽  
Intestinal Intraepithelial Lymphocytes ◽  
Histocompatibility Complex ◽  
Nonclassical Mhc ◽  
Mhc Class I Molecules

Intestinal intraepithelial lymphocytes (IELs) in mice include two main subsets of TCR-α/β1 cells which differ functionally and ontogenically from each other. One expresses the CD8α/α homodimer, whereas the other expresses the CD8α/β heterodimer. Although the presence of all CD8+TCR-α/β1 IELs is dependent on β2-microglobulin molecules, the nature of the major histocompatibility complex (MHC) class I molecules recognized by the CD8α/α and the CD8α/β1 subsets has remained elusive. Using mutant mice lacking the expression of both H2-Kb and H2-Db, we show that the CD8α/β1TCR-α/β1 subset is dependent on K or D molecules, whereas the CD8α/α1TCR-α/β1 subset is independent of classical MHC class I molecules. Furthermore, the CD8α/α1 cells are conserved in mice lacking expression of CD1, a nonclassical MHC class I–like molecule previously proposed to be a potential ligand for IELs. Using transporter associated with antigen processing (TAP)-deficient mice, this cell population can be further separated into a TAP-dependent and a TAP-independent subset, suggesting either the recognition of two nonclassical MHC-like molecules, only one of which is TAP dependent, or the involvement of a single nonclassical MHC-like molecule that is only partially TAP dependent. These findings demonstrate that CD8α/β1TCR-α/β1 IELs are restricted by H-2K and H-2D molecules, whereas the unusual subset of CD8α/α1TCR-α/β1 resident IELs recognize nonclassical MHC class I–like molecules that are distinct from CD1.

scholarly journals Analysis of Major Histocompatibility Complex Class I, TAP Expression, and LMP2 Epitope Sequence in Epstein-Barr Virus–Positive Hodgkin's Disease

Blood ◽  
1998 ◽  
Vol 92 (7) ◽  
pp. 2477-2483 ◽  
Author(s):  
Paul G. Murray ◽  
Christothea M. Constandinou ◽  
John Crocker ◽  
Lawrence S. Young ◽  
Richard F. Ambinder
Keyword(s):  
Major Histocompatibility Complex ◽  
Mhc Class I ◽  
Epstein Barr Virus ◽  
Class I ◽  
Major Histocompatibility ◽  
Barr Virus ◽  
Histocompatibility Complex ◽  
Epstein Barr ◽  
Hla A2.1 ◽  
Mhc Class I Molecules

Abstract The Epstein-Barr virus (EBV)-encoded latent membrane proteins, LMP1 and LMP2, are consistently expressed by the malignant Hodgkin/Reed-Sternberg (HRS) cells of EBV-associated Hodgkin's disease (HD). Cytotoxic T lymphocyte (CTL) responses to both of these proteins have been shown in the blood of EBV-seropositive individuals, yet in HD the apparent failure of the CTL response to eliminate HRS cells expressing LMP1 and LMP2 in vivo has given rise to the suggestion that HD may be characterized by the presence of defects in antigen processing/presentation or in CTL function. This study has used immunohistochemistry to show high-level expression of major histocompatibility complex (MHC) class I molecules by the HRS cells of EBV-associated HD and either low level or absence of expression of MHC class I molecules on HRS cells of EBV-negative tumors. In addition, HRS cells expressed high levels of transporter-associated proteins (TAP-1, -2), irrespective of the presence of latent EBV infection. These results suggest that global downregulation of MHC class I molecules does not account for the apparent ability of EBV-infected HRS cells to evade CTL responses, but may be important in the understanding of EBV-negative disease.We have also sequenced an epitope in LMP2A (CLGGLLTMV) that is restricted through HLA A2.1, a relatively common allele in Caucasian populations, and showed that this epitope is wild type in a small group of EBV-associated HLA A2.1-positive HD tumors. This result may be relevant to proposed immunotherapeutic approaches for EBV-positive HD patients that target CTL epitopes.

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