0000000000997320
AUTHOR
Dorothea Gillert-marien
The Immune Evasion Paradox: Immunoevasins of Murine Cytomegalovirus Enhance Priming of CD8 T Cells by Preventing Negative Feedback Regulation▿
ABSTRACTCytomegaloviruses express glycoproteins that interfere with antigen presentation to CD8 T cells. Although the molecular modes of action of these “immunoevasins” differ between cytomegalovirus species, the convergent biological outcome is an inhibition of the recognition of infected cells. In murine cytomegalovirus, m152/gp40 retains peptide-loaded major histocompatibility complex class I molecules in acis-Golgi compartment, m06/gp48 mediates their vesicular sorting for lysosomal degradation, and m04/gp34, although not an immunoevasin in its own right, appears to assist in the concerted action of all three molecules. Using the Ld-restricted IE1 epitope YPHFMPTNL in the BALB/c mouse m…
Cytomegalovirus Encodes a Positive Regulator of Antigen Presentation
ABSTRACT Murine cytomegalovirus encodes three regulators of antigen presentation to antiviral CD8 T cells. According to current paradigms, all three regulators are committed to the inhibition of the presentation of antigenic peptides. Whereas m152/gp40 catalyzes the retention of peptide-loaded major histocompatibility complex (MHC) class I molecules in a cis -Golgi compartment, m06/gp48 binds stably to class I molecules and directs them into the cellular cargo-sorting pathway of lysosomal degradation. Regulator m04/gp34 also binds stably to class I molecules, but unlike m152 and m06, it does not downmodulate MHC class I cell surface expression. It has entered the literature as a direct inhi…
TCR-Ligand koff rate correlates with the protective capacity of antigen-specific CD8+ T cells for adoptive transfer.
Adoptive immunotherapy is a promising therapeutic approach for the treatment of chronic infections and cancer. Thereby, T cells within a certain range of high avidity for their cognate ligand are believed to be most effective. T cell receptor (TCR) transfer experiments indicate that a major part of avidity is hard-wired within the structure of the TCR. Unfortunately, rapid measurement of structural avidity of TCRs is difficult on living T cells. We developed a technology, where dissociation (koff-rate) of truly monomeric peptide major histocompatibility complex (pMHC) molecules bound to surface expressed TCRs can be monitored by real-time microscopy in a highly reliable manner. A first eval…