Polymorphisms in MHC class I molecules influence their interactions with components of the antigen processing and presentation pathway

2021 ◽  
Author(s):  
Aure Aflalo ◽  
Louise H. Boyle
Keyword(s):  
Mhc Class I ◽  
Antigen Processing ◽  
Class I ◽  
Presentation Pathway ◽  
Antigen Processing And Presentation ◽  
Mhc Class I Molecules

scholarly journals Relevance of viral context and diversity of antigen-processing routes for respiratory syncytial virus cytotoxic T-lymphocyte epitopes

2008 ◽  
Vol 89 (9) ◽  
pp. 2194-2203 ◽  
Author(s):  
Carolina Johnstone ◽  
Sara Guil ◽  
Miguel A. Rico ◽  
Blanca García-Barreno ◽  
Daniel López ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Mhc Class I ◽  
Antigen Processing ◽  
Cytotoxic T Lymphocyte ◽  
Class I ◽  
F Protein ◽  
Mhc Class I Molecule ◽  
Presentation Pathway ◽  
Syncytial Virus ◽  
In Cells

Antigen processing of respiratory syncytial virus (RSV) fusion (F) protein epitopes F85–93 and F249–258 presented to cytotoxic T-lymphocytes (CTLs) by the murine major histocompatibility complex (MHC) class I molecule Kd was studied in different viral contexts. Epitope F85–93 was presented through a classical endogenous pathway dependent on the transporters associated with antigen processing (TAP) when the F protein was expressed from either RSV or recombinant vaccinia virus (rVACV). At least in cells infected with rVACV encoding either natural or cytosolic F protein, the proteasome was required for epitope processing. In cells infected with rVACV encoding the natural F protein, an additional endogenous TAP-independent presentation pathway was found for F85–93. In contrast, epitope F249–258 was presented only through TAP-independent pathways, but presentation was brefeldin A sensitive when the F protein was expressed from RSV, or mostly resistant when expressed from rVACV. Therefore, antigen-processing pathways with different mechanisms and subcellular localizations are accessible to individual epitopes presented by the same MHC class I molecule and processed from the same protein but in different viral contexts. This underscores both the diversity of pathways available and the influence of virus infection on presentation of epitopes to CTLs.

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 Identification of human cancers deficient in antigen processing.

1993 ◽  
Vol 177 (2) ◽  
pp. 265-272 ◽  
Author(s):  
N P Restifo ◽  
F Esquivel ◽  
Y Kawakami ◽  
J W Yewdell ◽  
J J Mulé ◽  
...  
Keyword(s):  
T Cells ◽  
Endoplasmic Reticulum ◽  
Mhc Class I ◽  
Cell Lines ◽  
Antigen Processing ◽  
Human Tumor ◽  
Class I ◽  
Cell Lung Carcinoma ◽  
Mhc Molecules ◽  
Mhc Class I Molecules

Intracellular antigens must be processed before presentation to CD8+ T cells by major histocompatibility complex (MHC) class I molecules. Using a recombinant vaccinia virus (Vac) to transiently express the Kd molecule, we studied the antigen processing efficiency of 26 different human tumor lines. Three cell lines, all human small cell lung carcinoma, consistently failed to process endogenously synthesized proteins for presentation to Kd-restricted, Vac-specific T cells. Pulse-chase experiments showed that MHC class I molecules were not transported by these cell lines from the endoplasmic reticulum to the cell surface. This finding suggested that peptides were not available for binding to nascent MHC molecules in the endoplasmic reticulum. Northern blot analysis of these cells revealed low to nondetectable levels of mRNAs for MHC-encoded proteasome components LMP-7 and LMP-2, as well as the putative peptide transporters TAP-1 and TAP-2. Treatment of cells with interferon gamma enhanced expression of these mRNAs and reversed the observed functional and biochemical deficits. Our findings suggest that downregulation of antigen processing may be one of the strategies used by tumors to escape immune surveillance. Potential therapeutic applications of these findings include enhancing antigen processing at the level of the transcription of MHC-encoded proteasome and transporter genes.

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.

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