Cytomegalovirus Misleads Its Host by Priming of CD8 T Cells Specific for an Epitope Not Presented in Infected Tissues

Abstract

Cytomegaloviruses (CMVs) code for several proteins that inhibit the presentation of antigenic peptides to CD8 T cells. Although the molecular mechanisms of CMV interference with the major histocompatibility complex class I pathway are long understood, surprisingly little evidence exists to support a role in vivo. Here we document the first example of the presentation of an antigenic peptide being blocked by a CMV immune evasion protein in organs relevant to CMV disease. Although this D b -restricted peptide, which is derived from the antiapoptotic protein M45 of murine CMV (mCMV), is classified as an immunodominant peptide based on response magnitude and long-term memory, adoptive transfer of M45 epitope-specific CD8 T cells did not protect against infection with wild-type mCMV. Notably, the same cells protected C57BL/6 mice infected with an mCMV mutant in which immune evasion protein m152/gp40 is deleted. These data indicate that direct presentation or cross-presentation of an antigenic peptide by professional antigen-presenting cells can efficiently prime CD8 T cells that fail in protection against CMV organ disease because m152/gp40 prevents presentation of this peptide in pathogenetically relevant tissue cells.

FliC-Specific CD4+ T Cell Responses Are Restricted by Bacterial Regulation of Antigen Expression

“…We propose that repression of protective Ags like FliC, in concert with other genetically co-coordinated modifications of the bacterial surface (37), could facilitate bacterial growth in vivo by affording virulent Salmonella the opportunity for additional rounds of replication before the onset of effective adaptive immune recognition. A similar "decoy and delay" strategy is used during successful CMV infection: the dominant CD8 ϩ T cell response is directed toward an epitope not presented in infected tissues in vivo (73).…”

CD4+T-Cell Reconstitution Reduces Cytomegalovirus in the Immunocompromised Brain

“…Priming of nonfunctional CD8 ϩ T cells is also reported, thereby misleading the host defense response (20). The priming method used in our studies may have limited the number of epitopes for lymphocyte response and skewed recognition to IE1 proteins and m164 gene product (13,50), as these are the major immunodominant responses against live virus infection in healthy hosts.…”

Refinement of strategies for the development of a human cytomegalovirus dense body vaccine

“…However, logistic limitations and the possible risk of transfer of alloreactive cells together with HCMV speciWc cells have prevented introduction of such strategies as a clinical routine. T cell receptor (TCR-) based ex vivo sorting of antiviral CD8 T cells and subsequent adoptive transfer of such cells has been shown to be eVective to V. Mersseman · V. Böhm · R. Holtappels · P. Deegen ·reduce the incidence of cytomegalovirus induced disease in a mouse model [15,16], and it has also been applied in Wrst clinical studies [10]. However, a number of questions regarding the adoptive transfer of HCMV-speciWc T lymphocytes remain unanswered.…”