Question 2: When testing your mouse colonies for susceptibility to a variety of

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Question 2: When testing your mouse colonies for susceptibility to a variety of pathogens, you come across several strains of the virus MSSV (Murine Sleeping Sickness Virus - which causes the mice to sleep 23 hours out of the day) and the bacterium B. spinialis (which makes them run in counter-clockwise circles) that seem to escape activating T cell responses. After studying these pathogen strains, you identify that they avoid activating T cells by blocking various steps in antigen processing and presentation a. (2 points) MSSV strain 1 (MSSV1) does not generate any Tc response. You find that the levels of MHC class I on infected cells is greatly reduced. Name two specific places in the MHC I presentation path where the virus could be disrupting MHC I expression. b. (1 point) MSSV strain 6 (MSSV6) also doesn't activate T cells. However, you find that levels of MHC class I expression on the surface are normal. Name one way MSSV6 could avoid presentation of viral peptides without affecting levels of class I MHC. c. (2 points) B. spinialis strain 4 does not activate class lI-restricted TH responses. Also, the level of class Il on the cell surface of macrophages that have phagocytosed strain 4 is lowered drastically. Name two specific steps at which this strain could be interfering with class II formation

Explanation / Answer

a. Major Histocompatibility Complex I (MHC I) bearing cells, utilize the general intracellular protein turnover pathway, to process endogenous antigens and present them through the MHC I molecules.

The cytosolic proteolytic system, including the proteolytic complex called the proteasome, target the intracellular proteins. To tag the proteins to be attacked by proteasomes, the proteins to be degraded marked by association with ubiquitin. The proteasome complex ca degrades the ubiquitin associated proteins into smaller amino acid chains.

The degrade peptides, are the transported to the rough endoplasmic reticulum (RER), by transporter protein called transporter associated with antigen processing (TAP1 and TAP2). The MHCI molecules components ( chains and 2microglobulin) are synthesized in the polysomes, associated with RER. The TAP associates with the pre-degraded cytosolic peptide and transport it to RER> Where they associate with MHC I components ad facilitates their folding with the antigenic peptide.

Certain strain of the viruses, can control the activity and the TAP function and prevent the association of peptide with TAP. The formation of MHC peptide complex, may be disrupted by preventing the translocation of cytosolic peptide to RER.

Further the virus, may also facilitate the endocytosis or cleavage of MHC I molecules by facilitating their ubiquitination.

b. Certain strain of the virus may not disrupt the MHC class I molecule formation and the biosynthesis of MHC I may be normal, in the virus invaded cell. They may still evade the peptide presentation by MHC I molecules by controlling the function of proteasome complex.

c. The strain could interfere in MHC II formation by two possible ways. The most important mechanism involves, blocking interferon- (IFN-) signal transduction. This disrupts the and expression of the MHC class II transactivator.

Further, virus inhibit the MHC II antigen prentation pathway by controlling the stability and sorting of the antigen molecules.

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