Startseite
Podcasts
Medizin - Open Access LMU - Teil 11/22 Podcast
Restoration of cytomegalovirus antigen presentation by gamma interferon combats viral escape.

Restoration of cytomegalovirus antigen presentation by gamma interferon combats viral escape.

Medizin - Open Access LMU - Teil 11/22 vor 32 Jahren

0:00

An immediate-early protein of murine cytomegalovirus (MCMV), pp89,
elicits an immunodominant and protective major histocompatibility
complex (MHC) class I Ld-restricted CD8+ T-lymphocyte response.
Remarkably, presentation of the naturally processed peptide of
pp89, the nonapeptide YPHFMPTNL, is abolished during permissive
MCMV infection in vitro. This defect in pp89 presentation is due to
the expression of MCMV early gene functions that specifically block
the transport of peptide-charged MHC class I complexes to the cell
surface (M. Del Val, H. Hengel, H. Häcker, U. Hartlaub, T. Ruppert,
P. Lucin, and U. H. Koszinowski, J. Exp. Med. 176:729-738, 1992).
Here, we demonstrate that MCMV-specific CD8+ T lymphocytes can
reconstitute pp89 presentation in a parakrine fashion. The
lymphocytes mediate the restoration of antigen presentation by
MCMV-infected cells by releasing gamma interferon (IFN-gamma).
IFN-gamma has no effect on synthesis and stability of the viral
antigen pp89 nor does it interfere with the expression of viral
early genes and their inhibitory effect on MHC class I molecular
maturation. IFN-gamma results in a 25-fold increase in the
synthesis of MHC class I molecules and a similar increase in the
abundance of pp89-derived peptide. Many of the MHC molecules remain
retained by the viral effect, but a surplus of MHC molecules
escapes the effect and provides the effective surface presentation
of the peptide. Adoptive cell transfer studies demonstrate the
IFN-gamma dependence of CD8+ T-lymphocyte function in vivo.
Altogether, these data reconcile the paradoxical findings of an
impaired pp89 presentation in vitro in parallel with pp89-specific
CD8+ T-cell protection in vivo. The results also imply a role of
IFN-gamma in the T-lymphocyte-mediated control of cytomegalovirus
infection. The known propensity of cytomegalovirus to cause serious
disease in the immunocompromised host is discussed in the light of
these findings