scholarly journals Chlamydia trachomatisImmune Evasion via Downregulation of MHC Class I Surface Expression Involves Direct and Indirect Mechanisms

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Joyce A. Ibana ◽  
Danny J. Schust ◽  
Jun Sugimoto ◽  
Takeshi Nagamatsu ◽  
Sheila J. Greene ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Mhc Class I ◽  
Mhc Class Ii ◽  
Surface Expression ◽  
Class I ◽  
Cell Surface Expression ◽  
Class I Mhc ◽  
Pathogen Entry ◽  
Antigen Presenting ◽  
Immune Detection

GenitalC. trachomatisinfections typically last for many months in women. This has been attributed to several strategies by whichC. trachomatisevades immune detection, including well-described methods by whichC. trachomatisdecreases the cell surface expression of the antigen presenting molecules major histocompatibility complex (MHC) class I, MHC class II, and CD1d in infected genital epithelial cells. We have harnessed new methods that allow for separate evaluation of infected and uninfected cells within a mixed population of chlamydia-infected endocervical epithelial cells to demonstrate that MHC class I downregulation in the presence ofC. trachomatisis mediated by direct and indirect (soluble) factors. Such indirect mechanisms may aid in priming surrounding cells for more rapid immune evasion upon pathogen entry and help promote unfettered spread ofC. trachomatisgenital infections.

scholarly journals Variations in MHC class I antigen presentation and immunopeptidome selection pathways

F1000Research ◽  
2020 ◽  
Vol 9 ◽  
pp. 1177
Author(s):  
Anita J. Zaitouna ◽  
Amanpreet Kaur ◽  
Malini Raghavan
Keyword(s):  
Cell Surface ◽  
Antigen Presentation ◽  
Surface Expression ◽  
Structural Features ◽  
Class I ◽  
Cell Surface Expression ◽  
Immune Recognition ◽  
Antigen Receptors ◽  
Class I Mhc ◽  
Mhc I

Major histocompatibility class I (MHC-I) proteins mediate immunosurveillance against pathogens and cancers by presenting antigenic or mutated peptides to antigen receptors of CD8+ T cells and by engaging receptors of natural killer (NK) cells. In humans, MHC-I molecules are highly polymorphic. MHC-I variations permit the display of thousands of distinct peptides at the cell surface. Recent mass spectrometric studies have revealed unique and shared characteristics of the peptidomes of individual MHC-I variants. The cell surface expression of MHC-I–peptide complexes requires the functions of many intracellular assembly factors, including the transporter associated with antigen presentation (TAP), tapasin, calreticulin, ERp57, TAP-binding protein related (TAPBPR), endoplasmic reticulum aminopeptidases (ERAPs), and the proteasomes. Recent studies provide important insights into the structural features of these factors that govern MHC-I assembly as well as the mechanisms underlying peptide exchange. Conformational sensing of MHC-I molecules mediates the quality control of intracellular MHC-I assembly and contributes to immune recognition by CD8 at the cell surface. Recent studies also show that several MHC-I variants can follow unconventional assembly routes to the cell surface, conferring selective immune advantages that can be exploited for immunotherapy.

Expression of MHC class I, MHC class II, and cancer germline antigens in neuroblastoma

2004 ◽  
Vol 54 (4) ◽  
pp. 400-406 ◽  
Author(s):  
Matthias W�lfl ◽  
Achim A. Jungbluth ◽  
Federico Garrido ◽  
Teresa Cabrera ◽  
Sharon Meyen-Southard ◽  
...  
Keyword(s):  
Mhc Class I ◽  
Mhc Class Ii ◽  
Class Ii ◽  
Class I ◽  
Class I Mhc ◽  
Cancer Germline

scholarly journals The Major Histocompatibility Complex of Old World Camels—A Synopsis

Cells ◽  
2019 ◽  
Vol 8 (10) ◽  
pp. 1200 ◽  
Author(s):  
Plasil ◽  
Wijkmark ◽  
Elbers ◽  
Oppelt ◽  
Burger ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
Mhc Class I ◽  
Mhc Class Ii ◽  
Class Ii ◽  
Class I ◽  
Class Iii ◽  
Old World ◽  
Histocompatibility Complex ◽  
Mhc Class Iii ◽  
Antigen Presenting

This study brings new information on major histocompatibility complex (MHC) class III sub-region genes in Old World camels and integrates current knowledge of the MHC region into a comprehensive overview for Old World camels. Out of the MHC class III genes characterized, TNFA and the LY6 gene family showed high levels of conservation, characteristic for MHC class III loci in general. For comparison, an MHC class II gene TAP1, not coding for antigen presenting molecules but functionally related to MHC antigen presenting functions was studied. TAP1 had many SNPs, even higher than the MHC class I and II genes encoding antigen presenting molecules. Based on this knowledge and using new camel genomic resources, we constructed an improved genomic map of the entire MHC region of Old World camels. The MHC class III sub-region shows a standard organization similar to that of pig or cattle. The overall genomic structure of the camel MHC is more similar to pig MHC than to cattle MHC. This conclusion is supported by differences in the organization of the MHC class II sub-region, absence of functional DY genes, different organization of MIC genes in the MHC class I sub-region, and generally closer evolutionary relationships of camel and porcine MHC gene sequences analyzed so far.

scholarly journals Tumorigenic Adenovirus Type 12 E1A Inhibits Phosphorylation of NF-κB by PKAc, Causing Loss of DNA Binding and Transactivation

2007 ◽  
Vol 82 (1) ◽  
pp. 40-48 ◽  
Author(s):  
Hancheng Guan ◽  
Junfang Jiao ◽  
Robert P. Ricciardi
Keyword(s):  
Dna Binding ◽  
Human Adenovirus ◽  
Adenovirus Type ◽  
Surface Expression ◽  
Class I ◽  
Cell Surface Expression ◽  
Class I Mhc ◽  
Mhc I ◽  
Histocompatibility Complex ◽  
Tumorigenic Cells

ABSTRACT Human adenovirus type 12 (Ad12) E1A protein (E1A-12) is the key determinant of viral tumorigenesis. E1A-12 mediates major histocompatibility complex class I (MHC-I) shutoff by inhibiting the DNA binding of the transcriptional activator NF-κB (p50/p65) to the class I enhancer. This enables Ad12 tumorigenic cells to avoid class I recognition and lysis by cytotoxic T lymphocytes. In this study, we demonstrate that the phosphorylation of p50 and p65 by the catalytic subunit of protein kinase A (PKAc) is essential for NF-κB DNA binding and transactivation activity. Treatment with H89 and knockdown of PKAc in cells led to the inhibition of phosphorylation at p50 Ser337 and p65 Ser276 and loss of DNA binding by NF-κB. Importantly, NF-κB phosphorylation by PKAc was repressed by tumorigenic E1A-12, but not by nontumorigenic Ad5 E1A (E1A-5). The stable introduction of E1A-12 into Ad5 nontumorigenic cells resulted in a decrease in the phosphorylation of NF-κB, loss of NF-κB DNA binding, and the failure of NF-κB to activate a target promoter, as well as diminution of MHC-I transcription and cell surface expression. Significantly, the amount and enzymatic activity of PKAc were not altered in Ad12 tumorigenic cells relative to its amount and activity in nontumorigenic Ad5 cells. These results demonstrate that E1A-12 specifically prevents NF-κB from being phosphorylated by PKAc.

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.

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