Open AccessMonofunctional and Polyfunctional CD8+T Cell Responses to Human Herpesvirus 8 Lytic and Latency Proteins
Author(s) -
Lauren M. Lepone,
Giovanna Rappocciolo,
Emilee R. Knowlton,
Mariel Jais,
Paolo Piazza,
Frank J. Jenkins,
Charles R. Rinaldo
Publication year - 2010
Publication title -
clinical and vaccine immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.649
H-Index - 77
eISSN - 1556-6811
pISSN - 1556-679X
DOI - 10.1128/cvi.00189-10
Subject(s) - epitope , virology , cytotoxic t cell , biology , cd8 , lytic cycle , antigen , major histocompatibility complex , degranulation , mhc class i , primary effusion lymphoma , t cell , microbiology and biotechnology , immunology , virus , immune system , biochemistry , receptor , in vitro
Human herpesvirus 8 (HHV-8) is the etiological agent of Kaposi's sarcoma, primary effusion lymphoma, and multicentric Castleman's disease. It is postulated that CD8+ T cell responses play an important role in controlling HHV-8 infection and preventing development of disease. In this study, we investigated monofunctional and polyfunctional CD8+ T cell responses to HHV-8 lytic proteins gB (glycoprotein B) and K8.1 and latency proteins LANA-1 (latency-associated nuclear antigen-1) and K12. On the basis of our previous findings that dendritic cells (DC) reveal major histocompatibility complex (MHC) class I epitopes in gB, we used a DC-based system to identify 2 novel epitopes in gB, 2 in K8.1, 5 in LANA-1, and 1 in K12. These new HHV-8 epitopes activated monofunctional and polyfunctional CD8+ T cells that produced various combinations of gamma interferon, interleukin 2, tumor necrosis factor alpha, macrophage inhibitory protein 1β, and cytotoxic degranulation marker CD107a in healthy HHV-8-seropositive individuals. We were also able to detect HHV-8-specific CD8+ T cells in peripheral blood samples using HLA A*0201 pentamer complexes for one gB epitope, one K8.1 epitope, two LANA-1 epitopes, and one K12 epitope. These immunogenic regions of viral lytic and latency proteins could be important in T cell control of HHV-8 infection.