The antiviral efficacy of simian immunodeficiency virus-specific CD8+ T cells is unrelated to epitope specificity and is abrogated by viral escape.
CD8(+) T lymphocytes appear to play a role in controlling human immunodeficiency virus (HIV) replication, yet routine immunological assays do not measure the antiviral efficacy of these cells. Furthermore, it has been suggested that CD8+ T cells that recognize epitopes derived from proteins expressed early in the viral replication cycle can be highly efficient. We used a functional in vitro assay to assess the abilities of different epitope-specific CD8+ T-cell lines to control simian immunodeficiency virus (SIV) replication. We compared the antiviral efficacies of 26 epitope-specific CD8+ T-cell lines directed against seven SIV epitopes in Tat, Nef, Gag, Env, and Vif that were restricted by either Mamu-A*01 or Mamu-A*02. Suppression of SIV replication varied depending on the epitope specificities of the CD8+ T cells and was unrelated to whether the targeted epitope was derived from an early or late viral protein. Tat(28-35)SL8- and Gag(181-189)CM9-specific CD8+ T-cell lines were consistently superior at suppressing viral replication compared to the other five SIV-specific CD8+ T-cell lines. We also investigated the impact of viral escape on antiviral efficacy by determining if Tat(28-35)SL8- and Gag(181-189)CM9-specific CD8+ T-cell lines could suppress the replication of an escaped virus. Viral escape abrogated the abilities of Tat(28-35)SL8- and Gag(181-189)CM9-specific CD8+ T cells to control viral replication. However, gamma interferon (IFN-gamma) enzyme-linked immunospot and IFN-gamma/tumor necrosis factor alpha intracellular-cytokine-staining assays detected cross-reactive immune responses against the Gag escape variant. Understanding antiviral efficacy and epitope variability, therefore, will be important in selecting candidate epitopes for an HIV vaccine.
Loffredo
John T
JT
Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, 555 Science Drive, Madison, WI 53711, USA.
Burwitz
Benjamin J
BJ
Rakasz
Eva G
EG
Spencer
Sean P
SP
Stephany
Jason J
JJ
Vela
Juan Pablo Giraldo
JP
Martin
Sarah R
SR
Reed
Jason
J
Piaskowski
Shari M
SM
Furlott
Jessica
J
Weisgrau
Kim L
KL
Rodrigues
Denise S
DS
Soma
Taeko
T
Napoé
Gnankang
G
Friedrich
Thomas C
TC
Wilson
Nancy A
NA
Kallas
Esper G
EG
Watkins
David I
DI
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D002478:Cells, Cultured; D003429:Cross Reactions; D004797:Enzyme-Linked Immunosorbent Assay; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D015683:Gene Products, gag / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D008253:Macaca mulatta; D017354:Point Mutation; D012367:RNA, Viral / Q000097:blood; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D013601:T-Lymphocytes / Q000737:chemistry / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism; D019562:Viral Load; D014779:Virus Replication / Q000235:genetics / Q000276:immunology
D018984:Epitopes, T-Lymphocyte; D015683:Gene Products, gag; D012367:RNA, Viral; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma