The ESAT-6 Protein of Interacts with Beta-2-Microglobulin (β2M) Affecting Antigen Presentation Function of Macrophage

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M. tuberculosis is a dangerous and highly successful pathogen that has evolved several mechanisms to manipulate the host immune regulatory network. Proteins secreted by M. tuberculosis play important roles in virulence. One such protein is ESAT-6, which is secreted along with its chaperone CFP-10. Despite a host of studies highlighting modulation of immune responses by ESAT-6, there have not been many that identified host proteins interacting with ESAT-6. We have now found that the host protein β2M interacts very specifically with ESAT-6 at its C-terminal region. The soluble ESAT-6:CFP-10 complex was found to be trafficked into the endoplasmic reticulum, and treatment with recombinant ESAT-6:CFP-10 or the over-expression of ESAT-6 reduced cell surface expression of β2M and molecules which remain associated with it like HLA-I. Recombinant ESAT-6:CFP-10 was also found to reduce classical and cross presentation of peptide antigens by MHC-I molecules. In summary, our data indicate that interaction between ESAT-6 and β2M can reduce the levels of available free β2M that associate with HLA/MHC-I molecules. This could be an interesting mechanism by which M. tuberculosis inhibits classical and cross presentation of peptide antigens in order to prevent or delay the onset of anti-mycobacterial adaptive immune responses.

Vyšlo v časopise: The ESAT-6 Protein of Interacts with Beta-2-Microglobulin (β2M) Affecting Antigen Presentation Function of Macrophage. PLoS Pathog 10(10): e32767. doi:10.1371/journal.ppat.1004446
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004446

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