Cytomegalovirus (CMV) efficiently evades many host immune defenses and encodes a number of proteins that prevent antigen presentation by major histocompatibility complex class I (MHC-I) molecules in order to evade recognition and killing of infected cells by cytotoxic CD8(+) T cells. We recently showed that rhesus CMV-specific Rh178 intercepts MHC-I protein translation before interference of MH...

The presence of post-translational regulation of MHC class II (MHC II) under physiological conditions has been demonstrated recently in dendritic cells (DCs) that potently function as antigen-presenting cells (APCs). Here, we report that MARCH-I, an E3 ubiquitin ligase, plays a pivotal role in the post-translational regulation of MHC II in B cells. MARCH-I expression was particularly high in B ...

The major histocompatibility complex (MHC) class I region in mammals contains both classical and non-classical MHC class I genes. Classical MHC class I molecules present antigenic peptides to cytotoxic T lymphocytes, whereas non-classical MHC class I molecules have a variety of functions. Both classical and non-classical MHC molecules interact with natural killer cell receptors and may under so...

In B-lymphocytes, endocytosis of MHC I and MHC II molecules is important for the cross-priming and presentation of labile antigens, respectively. Here, we report that MHC I and MHC II were internalized by separate endocytic carriers that lacked transferrin receptor. Cholera toxin B was co-internalized with MHC II, but not with MHC I, suggesting that the CLIC/GEEC pathway is involved in the upta...

MARCH-I (membrane-associated RING-CH I) has been suggested as a physiological E3 ubiquitin ligase for both MHC class II (MHC II) and B7-2. In this study, we show that MARCH-I-mediated MHC II ubiquitination is necessary for the maintenance of conventional dendritic cell (cDC) functions in the steady state. MARCH-I-deficient cDCs accumulated MHC II and B7-2 and exhibited low Ag-presenting ability...

The MHC class I (MHC-I) region in New World monkeys (Platyrrhini) has remained relatively understudied. To evaluate the diversification patterns and transcription behavior of MHC-I in Platyrrhini, we first analyzed public genomic sequences from the MHC-G-like subregion in Saimiri boliviensis, Ateles geoffroyi and Callicebus moloch, and from the MHC-B subregion in Saimiri boliviensis. While S. b...

Nef, a regulatory protein of human and simian immunodeficiency viruses, downregulates cell surface expression of both class I MHC and CD4 molecules in T cells by accelerating their endocytosis. Fibroblasts were used to study alterations in the traffic of class I MHC complexes induced by Nef. We found that Nef downregulates class I MHC complexes by a novel mechanism involving the accumulation of...

Pancreatic ductal adenocarcinoma (PDAC) is among the world's deadliest cancers. Multiple studies demonstrated that PDAC frequently characterized by presence of Kirsten Rat Sarcoma (KRAS) G12D, G12V, and G12R protein mutants. The mutants are potential immunotherapy targets due to their as cancer-specific neoantigens. KRAS G12V contain vaccine-immunogenic epitopes. epitopes were presented at majo...

Murine cytomegalovirus (MCMV) interferes with the MHC class I pathway of antigen presentation. The type I transmembrane glycoprotein gp40, encoded by the gene m152, retains major histocompatibility complex (MHC) class I complexes in the endoplasmic reticulum (ER)-Golgi intermediate compartment (ERGIC)/cis-Golgi. These MHC class I complexes are stable, show an extended half-life and do not excha...