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Polycytokine responses by CD8+ T lymphocytes to KSHV/HHV8 lytic and latency proteins
Author(s) -
Lepone Lauren,
Knowlton Emilee,
Rappocciolo Giovanna,
Piazza Paolo,
Jais Mariel,
Rinaldo Charles
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1068.3
Subject(s) - lytic cycle , elispot , cd8 , epitope , virology , cytotoxic t cell , latency (audio) , biology , flow cytometry , glycoprotein , immunology , chemistry , microbiology and biotechnology , virus , immune system , antigen , genetics , in vitro , computer science , telecommunications
Objectives: Based on our previous findings that dendritic cells (DC) are required to reveal epitopes of human herpesvirus 8 (KSHV/HHV8) glycoprotein B (gB) (Blood 99:3360, 2002), we determined CD8 + T cell responses to multiple lytic and latency viral proteins. Methods: T cells were stimulated with DC from HHV8 seropositive, HLA A*0201 donors that were loaded with overlapping peptides derived from gB and K8.1 lytic proteins, and K12 and LANA latency proteins, and screened for IFNγ production by ELISPOT. Positive peptides were then assessed for production of IFNγ, IL2, TNFα, MIP1β and CD107a by flow cytometry. Results: Our DC‐T cell model revealed 5 gB, 4 K8.1, 2 K12 and 5 LANA HLA A*0201 epitopes. The HHV8 lytic and latency proteins induced predominately IFN‐γ, IL2 and CD107a. Conclusions: This is the first demonstration that HHV8 lytic and latency proteins induce polycytokine production by CD8 + T cells. These targeted regions of the virus could be critical in HHV8 immunopathogenesis and vaccine development. (U01‐AI35041, R01 CA82053)