A comparison of viral immune escape strategies targeting the MHC class I assembly pathway

Abstract

Peptide fragments from proteins of intracellular pathogens such as viruses are displayed at the cell surface by MHC class I molecules thus enabling surveillance by cytotoxic T cells. Peptides are produced in the cytosol by proteasomal degradation and translocated into the endoplasmic reticulum by the peptide transporter TAP. Empty MHC class I molecules associate with TAP prior to their acquisition of peptides, a process which is assisted and controlled by a series of chaperones. The first part of this review summarizes our current knowledge of this assembly pathway and describes recent observations that tapasin functions as an endoplasmic reticulum retention molecule for empty MHC class I molecules. To defeat the presentation of virus-derived peptides, several DNA viruses have devised strategies to interfere with MHC class I assembly. Although these evasion strategies have evolved independently and differ mechanistically they often target the same step in this pathway. We compare escape mechanisms of different viruses with particular emphasis on the retention of newly synthesized MHC class I molecules in the endoplasmic reticulum and the inhibition of peptide transport by viral proteins.

Dynamic Antigen Presentation Patterns of Listeria monocytogenes-Derived CD8 T Cell Epitopes In Vivo

“…In contrast to acidic peptide extraction the Ag presentation assay detects selectively cell surface peptide presentation. This is an important advantage if the relevance of Ag presentation for the induction of T cells shall be studied because some microbial immune escape mechanisms selectively prevent cell surface presentation of antigenic peptides (20). However, after infection of mice with L. monocytogenes, the peptide presentation patterns of splenocytes and infected cell lines were principally confirmed by peptide extraction of whole organs and cells, respectively.…”

Alcohol and HIV decrease proteasome and immunoproteasome function in macrophages: implications for impaired immune function during disease

“…PR activity is up-regulated by pro-inflammatory cytokines [interferon (IFN)-c TNF-a and IL-6] [20,22]. After IFN-c stimulation, constitutive PR subunits X, Y, and Z are replaced by inducible PR subunits LMP2, LMP7, and MELC-1 [20,21]. Processing of protein antigens within inducible subunits of IPR is important in subsequent conjugation with the class I major histocompatibility complex (MHC) required for antigen presentation [21,23].…”

“…The PR consists of a 20S catalytic core that is activated by binding of the PA28 regulator [17][18][19]. PR constitutive subunits (X, Y, Z) possess chymotrypsin-like (X), trypsin-like (Y), and peptidyl-glutamyl-peptide hydrolase (Z) activities [20,21]. PR activity is up-regulated by pro-inflammatory cytokines [interferon (IFN)-c TNF-a and IL-6] [20,22].…”

“…PR constitutive subunits (X, Y, Z) possess chymotrypsin-like (X), trypsin-like (Y), and peptidyl-glutamyl-peptide hydrolase (Z) activities [20,21]. PR activity is up-regulated by pro-inflammatory cytokines [interferon (IFN)-c TNF-a and IL-6] [20,22]. After IFN-c stimulation, constitutive PR subunits X, Y, and Z are replaced by inducible PR subunits LMP2, LMP7, and MELC-1 [20,21].…”

Poxvirus Infection-Associated Downregulation of C-Type Lectin-Related-b Prevents NK Cell Inhibition by NK Receptor Protein-1B

“…The first and best described of these receptor systems is the inhibition of NK cells by classical and nonclassical MHC class I (MHC-I) proteins. This recognition system that senses missing self is believed to have evolved to allow NK cells to detect virus-infected cells, because many viruses interfere with normal expression of MHC-I proteins to evade T cell responses (3,4). The receptor systems for MHC-I have undergone considerable selective pressure and have diverged significantly between species, and this divergence is exemplified by the differences between humans and rodents.…”