MHC molecules (also known as major histocompatibility complex molecules) assist in the presentation of antigens to T cells in order to eradicate foreign pathogens. These molecules are highly polymorphic, meaning that they exist in multiple variants in order to avoid pathogens evading their activation of the immune response. MHC Class I molecules in particular deliver cytosolic peptides to the cell surface so that they can continue on through the cytosol and ultimately the endoplasmic reticulum (ER). The mechanisms by which different viruses invade our immune system are dynamic and specific to the genetic composition of the virus. An interesting virus in its process of immune evasion is the Herpes Simplex Virus Infection, given its ability to establish a lifelong cycle of dormant and active phases. Using a MHC Class I antibody is an effective tool to examine different approaches at virus evasion in the following experiments.
MHC Class I Antibody (OX18) [NB120-6405] - PC-12 cells were fixed for 10 minutes using 10% formalin and then permeabilized for 5 minutes using 1X TBS + 0.5% Triton-X100. The cells were incubated with anti-MHC Class I (OX18) NB120-6405 at a 1:100 dilution overnight at 4C and detected with an anti-mouse Dylight 488 (Green) at a 1:500 dilution. Actin was detected with Phalloidin 568 (Red) at a 1:200 dilution. Nuclei were counterstained with DAPI (Blue). Cells were imaged using a 40X objective.
Biborka Bereczky-Veress et al used an MHC Class I Antibody in their study of the influence of perineurial cells and TLR2 and TLR9 on the rare disease of Herpes Simplex encephalitis. In order to properly treat a virus it is important to understand how the virus is recognized by our innate immune system (if at all). First, they used primary antibodies to follow the HSV-1 infection in DA and PVG rats compared to controls, which was found to be activated and largely localized to the epineurium or the tissue surrounding nerve bundles. Coincidentally, an immunohistochemical analysis of these same sections using a MHC Class I antibody showed that MHC Class I staining was higher in the nerve fascicles in the PVG rats as well. They also produced data that suggested that rats that were more resistant to Herpes Simplex entry had a higher expression of TLR2 and TLR9, implying that there was more phagocytic activity present.
Orr et al took a more direct approach at Herpes Simplex I entry in a research study that points to the inhibition of MHC Class I as a virulence factor in this infection. The basis of this study falls on the established fact that herpes evasion prevents CD8 T cells from recognizing and killing infected cells by inhibiting the expression of MHC class I. Ultimately their findings showed that CD8 T-cell priming in mice infected with HSV is carried out by cross-priming, and that inhibition of MHC Class I may impact the CD8 T-cell response. In a similar approach, Neumann looked at the how the Herpes Simplex Virus Type 1 targets MHC Class II proteins using FITC conjugated MHC Class I and MHC Class II primary antibodies in Flow Cytometry. Right away, there was a marked decrease of MHCI and MHCII alongside induction of the Herpes Simplex virus. It was hypothesized that the MHCI peptides were stuck in the ER due to the impairment of TAP. Overall, this group demonstrated that the herpes simplex virus 1 infection strongly decreases the amount of B lymphoblastoid cells and manipulates the MHCII processing pathway.
Novus Biologicals offers MHC Class I reagents for your research needs including:
- PMID: 16201019
- PMID: 20806060
- PMID: 12960333