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Inhibition of NK cells by murine CMV-encoded class I MHC homologue m144

A Kubota1, S Kubota, H E Farrell

  • 1Terry Fox Laboratory, British Columbia Cancer Agency, British Columbia, Canada.

Cellular Immunology
|February 12, 1999
PubMed

Insights

Murine cytomegalovirus protein m144 partially inhibits natural killer (NK) cell activity. This viral protein interacts with a new receptor on NK cells, impacting immune responses.

Area of Science:

  • Immunology
  • Virology
  • Molecular Biology

Background:

  • Murine cytomegalovirus (CMV) protein m144 is structurally similar to class I MHC heavy chains.
  • It is hypothesized that m144 plays a role in regulating NK-cell-mediated immune responses.
  • Understanding m144's function is crucial for comprehending viral immune evasion strategies.

Purpose of the Study:

  • To investigate the in vitro effects of m144 on natural killer (NK) cell cytotoxicity.
  • To determine if m144 interacts with known NK cell inhibitory receptors.

Main Methods:

  • Transfection of cell lines with wild-type m144 or a m144-green fluorescence protein chimera.
  • Assessing m144 expression using anti-m144 mAb and fluorescence.
  • Measuring antibody-dependent cell-mediated cytotoxicity (ADCC) of IL-2-activated NK cells against m144-expressing cells.
  • Testing the effect of antibodies against known NK inhibitory receptors (Ly-49A, C, G, I).

Main Results:

  • Raji cells expressed significant levels of m144.
  • m144 expression partially inhibited the ADCC of IL-2-activated NK cells from both CMV-susceptible (BALB/c) and resistant (C57BL/6) mice.
  • The inhibitory effect of m144 was not blocked by antibodies against known Ly-49 receptors.

Conclusions:

  • Murine CMV protein m144 partially inhibits NK cell activity.
  • m144 likely interacts with a novel inhibitory receptor on NK cells, distinct from known Ly-49 receptors.
  • This suggests a new mechanism of viral immune modulation.

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