title: CD8 T cell-evasive functions of human cytomegalovirus display pervasive MHC allele specificity, complementarity, and cooperativity.
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.
authors.affiliation: 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.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Ameres
authors.affiliation: Institut für Virologie, Universitätsmedizin der Johannes-Gutenberg-Universität Mainz, 55131 Mainz, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Besold
authors.affiliation: Institut für Virologie, Universitätsmedizin der Johannes-Gutenberg-Universität Mainz, 55131 Mainz, Germany.
authors.forename: Bodo
authors.initials: B
authors.lastname: Plachter
authors.affiliation: 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.
authors.forename: Andreas
authors.initials: A
authors.lastname: Moosmann
mesh_terms: D000483:Alleles; D017951:Antigen Presentation / Q000235:genetics / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D002460:Cell Line; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology*; D006801:Humans; D057131:Immune Evasion; D008297:Male
chemical_list: D000956:Antigens, Viral; D015395:Histocompatibility Antigens Class I