1. Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), encodes
ID: 213058 • Letter: 1
Question
1. Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), encodes a virulence protein (ESAT-6, in complex with another virulence protein, CFP-10) that binds and sequesters B2-microglobulin (B2m) proteins in the endoplasmic reticulum of infected macrophages. The sequestered 2m does not bind HLA protein chains, preventing mature HLA-B2m protein complexes from reaching the cell surface. This can potentially suppress surface expression of HLA-A, -B, or -C MHCI; HLA-like CD1d; and HLA-like NKG2 ligands ULBP and MICA/B. A reference: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4214792/ A. (20pts.) Briefly explain why and how this might make the infected macrophage: Less / More / No Change (circle) in susceptibility to cytotoxic natural kller (NK) cell responses against TB? Less / More I No Change (circle) to activate natural killer T cells (NK-T) cell responses? Less/ More/ No Change (circle) to cytotoxic T lymphocyte (CTL) cell responses? Less / More /No Change (circle) to antibody-dependent cytotoxicity cell (ADCC) responses?
Explanation / Answer
Ans:
ESAT6 a virulence protein encoded by M. tuberculosis is known to bind and sequester b2-microglobulin which doesn't bind to HLA protein chains. This can lead to the reduction of HLA/MHC1 molecules.
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