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J Immunol. 2014 Jun 15;192(12):5894-905. doi: 10.4049/jimmunol.1302281. Epub 2014 May 7.

CD8 T cell-evasive functions of human cytomegalovirus display pervasive MHC allele specificity, complementarity, and cooperativity.

Author information

1
Klinische Kooperationsgruppe Immunonkologie, Medizinische Klinik III, Klinikum der Universität München, 81377 Munich, Germany; Abteilung Genvektoren, Helmholtz Zentrum München, 81377 Munich, Germany; German Center for Infection Research, 81675 Munich, Germany; and.
2
Institut für Virologie, Universitätsmedizin der Johannes-Gutenberg-Universität Mainz, 55131 Mainz, Germany.
3
Klinische Kooperationsgruppe Immunonkologie, Medizinische Klinik III, Klinikum der Universität München, 81377 Munich, Germany; Abteilung Genvektoren, Helmholtz Zentrum München, 81377 Munich, Germany; German Center for Infection Research, 81675 Munich, Germany; and andreas.moosmann@helmholtz-muenchen.de.

Abstract

Immunoevasive proteins ("evasins") of human CMV (HCMV) modulate stability and localization of MHC class I (MHC I) molecules, and their supply of antigenic peptides. However, it is largely unknown to what extent these evasins interfere with recognition by virus-specific CD8 T cells. We analyzed the recognition of HCMV-infected cells by a panel of CD8 T cells restricted through one of nine different MHC I allotypes. We employed a set of HCMV mutants deleted for three or all four of the MHC I modulatory genes US2, US3, US6, and US11. We found that different HCMV evasins exhibited different allotype-specific patterns of interference with CD8 T cell recognition of infected cells. In contrast, recognition of different epitopes presented by the same given MHC I allotype was uniformly reduced. For some allotypes, single evasins largely abolished T cell recognition; for others, a concerted action of evasins was required to abrogate recognition. In infected cells whose Ag presentation efficiency had been enhanced by IFN-γ pretreatment, HCMV evasins cooperatively impared T cell recognition for several different MHC I allotypes. T cell recognition and MHC I surface expression under influence of evasins were only partially congruent, underscoring the necessity to probe HCMV immunomodulation using specific T cells. We conclude that the CD8 T cell evasins of HCMV display MHC I allotype specificity, complementarity, and cooperativity.

PMID:
24808364
DOI:
10.4049/jimmunol.1302281
[Indexed for MEDLINE]
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