Monofunctional and polyfunctional CD8+ T cell responses to human herpesvirus 8 lytic and latency proteins.
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.
Lepone
Lauren
L
University of Pittsburgh Graduate School of Public Health, 130 DeSoto Street, Pittsburgh, PA 15261, USA.
Rappocciolo
Giovanna
G
Knowlton
Emilee
E
Jais
Mariel
M
Piazza
Paolo
P
Jenkins
Frank J
FJ
Rinaldo
Charles R
CR
D000956:Antigens, Viral / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D006023:Glycoproteins / Q000276:immunology*; D006801:Humans; D009687:Nuclear Proteins / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000276:immunology*; D014764:Viral Proteins / Q000276:immunology*
D000956:Antigens, Viral; D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D006023:Glycoproteins; C113454:K8.1 protein, Human herpesvirus 8; D009687:Nuclear Proteins; D014759:Viral Envelope Proteins; D014764:Viral Proteins; C116207:glycoprotein B, human herpesvirus 8; C120136:kaposin B protein, Human herpesvirus 8; C109540:latency-associated nuclear antigen