scholarly journals A Mechanistic Model for Predicting Cell Surface Presentation of Competing Peptides by MHC Class I Molecules

2018 ◽  
Vol 9 ◽  
Author(s):  
Denise S. M. Boulanger ◽  
Ruth C. Eccleston ◽  
Andrew Phillips ◽  
Peter V. Coveney ◽  
Tim Elliott ◽  
...  
Keyword(s):  
Cell Surface ◽  
Mhc Class I ◽  
Mechanistic Model ◽  
Class I ◽  
Mhc Class I Molecules

Ligand Design for Specific MHC Class I Molecules on the Cell Surface

2020 ◽  
Author(s):  
Xizheng Sun ◽  
Reika Tokunaga ◽  
Yoko Nagai ◽  
Ryo Miyahara ◽  
Akihiro Kishimura ◽  
...  
Keyword(s):  
Cell Surface ◽  
Mhc Class I ◽  
Targeted Delivery ◽  
Peptide Ligands ◽  
Class I ◽  
Class I Mhc ◽  
Mhc I ◽  
Histocompatibility Complex ◽  
High Binding Affinity ◽  
Mhc Class I Molecules

<p><a></a><a></a><a>We have validated that ligand peptides designed from antigen peptides could be used for targeting specific major histocompatibility complex class I (MHC-I)</a> molecules on cell surface. To design the ligand peptides, we used reported antigen peptides for each MHC-I molecule with high binding affinity. From the crystal structure of the peptide/MHC-I complexes, we determined a modifiable residue in the antigen peptides and replaced this residue with a lysine with an ε-amine group modified with functional molecules. The designed ligand peptides successfully bound to cells expressing the corresponding MHC-I molecules via exchange of peptides bound to the MHC-I. We demonstrated that the peptide ligands could be used to transport a protein or a liposome to cells expressing the corresponding MHC-I. The present strategy may be useful for targeted delivery to cells overexpressing MHC-I, which have been observed autoimmune diseases.</p>

scholarly journals Release from Endoplasmic Reticulum Matrix Proteins Controls Cell Surface Transport of MHC Class I Molecules

Traffic ◽  
2015 ◽  
Vol 16 (6) ◽  
pp. 591-603 ◽  
Author(s):  
Susanne Fritzsche ◽  
Esam T. Abualrous ◽  
Britta Borchert ◽  
Frank Momburg ◽  
Sebastian Springer
Keyword(s):  
Endoplasmic Reticulum ◽  
Cell Surface ◽  
Mhc Class I ◽  
Matrix Proteins ◽  
Class I ◽  
Surface Transport ◽  
Mhc Class I Molecules

scholarly journals Modulation of Transporter Associated with Antigen Processing (TAP)-Mediated Peptide Import into the Endoplasmic Reticulum by Flavivirus Infection

2001 ◽  
Vol 75 (12) ◽  
pp. 5663-5671 ◽  
Author(s):  
Frank Momburg ◽  
Arno Müllbacher ◽  
Mario Lobigs
Keyword(s):  
Endoplasmic Reticulum ◽  
Cell Surface ◽  
Mhc Class I ◽  
Antigen Processing ◽  
Surface Expression ◽  
Class I ◽  
Peptide Transport ◽  
Cell Surface Expression ◽  
Flavivirus Infection ◽  
Mhc Class I Molecules

ABSTRACT In contrast to many other viruses that escape the cellular immune response by downregulating major histocompatibility complex (MHC) class I molecules, flavivirus infection can upregulate their cell surface expression. Previously we have presented evidence that during flavivirus infection, peptide supply to the endoplasmic reticulum is increased (A. Müllbacher and M. Lobigs, Immunity 3:207–214, 1995). Here we show that during the early phase of infection with different flaviviruses, the transport activity of the peptide transporter associated with antigen processing (TAP) is augmented by up to 50%. TAP expression is unaltered during infection, and viral but not host macromolecular synthesis is required for enhanced peptide transport. This study is the first demonstration of transient enhancement of TAP-dependent peptide import into the lumen of the endoplasmic reticulum as a consequence of a viral infection. We suggest that the increased supply of peptides for assembly with MHC class I molecules in flavivirus-infected cells accounts for the upregulation of MHC class I cell surface expression with the biological consequence of viral evasion of natural killer cell recognition.

scholarly journals Cell Surface Expression of Major Histocompatibility Complex Class I Molecules Is Reduced in Hepatitis C Virus Subgenomic Replicon-Expressing Cells

2003 ◽  
Vol 77 (21) ◽  
pp. 11644-11650 ◽  
Author(s):  
Keith D. Tardif ◽  
Aleem Siddiqui
Keyword(s):  
Major Histocompatibility Complex ◽  
Hepatitis C ◽  
Cell Surface ◽  
Mhc Class I ◽  
Surface Expression ◽  
Protein Glycosylation ◽  
Class I ◽  
Cell Surface Expression ◽  
Histocompatibility Complex ◽  
Mhc Class I Molecules

ABSTRACT The hepatitis C virus (HCV) causes chronic hepatitis in most infected individuals by evading host immune defenses. In this investigation, we show that HCV-infected cells may go undetected in the immune system by suppressing major histocompatibility complex (MHC) class I antigen presentation to cytotoxic T lymphocytes. Cells expressing HCV subgenomic replicons have lower MHC class I cell surface expression. This is due to reduced levels of properly folded MHC class I molecules. HCV replicons induce endoplasmic reticulum (ER) stress (K. Tardif, K. Mori, and A. Siddiqui, J. Virol. 76:7453-7459, 2002), which results from a decline in protein glycosylation. Decreasing protein glycosylation can disrupt protein folding, preventing the assembly of MHC class I molecules. This results in the accumulation of unfolded MHC class I. Therefore, the persistence and pathogenesis of HCV may depend upon the ER stress-mediated interference of MHC class I assembly and cell surface expression.

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 The bovine papillomavirus oncoprotein E5 retains MHC class I molecules in the Golgi apparatus and prevents their transport to the cell surface

Oncogene ◽  
2002 ◽  
Vol 21 (51) ◽  
pp. 7808-7816 ◽  
Author(s):  
Barbara Marchetti ◽  
G Hossein Ashrafi ◽  
Emmanouella Tsirimonaki ◽  
Philippa M O'Brien ◽  
M Saveria Campo
Keyword(s):  
Golgi Apparatus ◽  
Cell Surface ◽  
Mhc Class I ◽  
Class I ◽  
Bovine Papillomavirus ◽  
Mhc Class I Molecules

scholarly journals CD99 Regulates the Transport of MHC Class I Molecules from the Golgi Complex to the Cell Surface

2001 ◽  
Vol 166 (2) ◽  
pp. 787-794 ◽  
Author(s):  
Hae Won Sohn ◽  
Young Kee Shin ◽  
Im-Soon Lee ◽  
Young Mee Bae ◽  
Young Ho Suh ◽  
...  
Keyword(s):  
Cell Surface ◽  
Mhc Class I ◽  
Golgi Complex ◽  
Class I ◽  
Mhc Class I Molecules

Tetrameric cell-surface MHC class I molecules

Nature ◽  
1992 ◽  
Vol 357 (6374) ◽  
pp. 164-167 ◽  
Author(s):  
Sudhir Krishna ◽  
Philippe Benaroch ◽  
Shiv Pillai
Keyword(s):  
Cell Surface ◽  
Mhc Class I ◽  
Class I ◽  
Mhc Class I Molecules

HFE cross-talks with the MHC class I antigen presentation pathway

Blood ◽  
2005 ◽  
Vol 106 (3) ◽  
pp. 971-977 ◽  
Author(s):  
Sérgio F. de Almeida ◽  
Isabel F. Carvalho ◽  
Carla S. Cardoso ◽  
João V. Cordeiro ◽  
Jorge E. Azevedo ◽  
...  
Keyword(s):  
Cell Surface ◽  
Mhc Class I ◽  
Mononuclear Cells ◽  
Hereditary Hemochromatosis ◽  
Class I ◽  
Cell Surface Expression ◽  
Peripheral Blood Mononuclear ◽  
Presentation Pathway ◽  
Peptide Loading ◽  
Mhc Class I Molecules

AbstractHFE is a protein known to be involved in iron metabolism; yet, other than its homology with major histocompatibility complex (MHC) class I molecules, it has not been described as having an immunologic function. Here we report that peripheral blood mononuclear cells (PBMCs) from patients with hereditary hemochromatosis (HH) carrying the C282Y mutation in HFE have reduced cell-surface expression of MHC class I due to an enhanced endocytosis rate of MHC class I molecules caused by premature peptide and β2-microglobulin dissociation. This faster turnover also leads to increased expression levels of cell-surface free class I heavy chains in mutant PBMCs. Biochemical analysis indicates an earlier peptide loading and endoplasmic reticulum maturation of MHC class I molecules in C282Y mutant cells. Thermostability assays further showed that in HFE mutants the MHC class I peptide loading gives rise to low-stability heterotrimers that dissociate prematurely during its intracellular traffic. The present results suggest the existence of an intriguing cross-talk between a particular HFE mutation and the classical MHC class I route. These findings constitute the first description of peptide presentation pathway abnormalities linked to HFE and provide additional evidence for the occurrence of immunologic defects in patients with HH.

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