Pol-specific CD8+ T cells recognize simian immunodeficiency virus-infected cells prior to Nef-mediated major histocompatibility complex class I downregulation.
Effective, vaccine-induced CD8+ T-cell responses should recognize infected cells early enough to prevent production of progeny virions. We have recently shown that Gag-specific CD8+ T cells recognize simian immunodeficiency virus-infected cells at 2 h postinfection, whereas Env-specific CD8+ T cells do not recognize infected cells until much later in infection. However, it remains unknown when other proteins present in the viral particle are presented to CD8+ T cells after infection. To address this issue, we explored CD8+ T-cell recognition of epitopes derived from two other relatively large virion proteins, Pol and Nef. Surprisingly, infected cells efficiently presented CD8+ T-cell epitopes from virion-derived Pol proteins within 2 h of infection. In contrast, Nef-specific CD8+ T cells did not recognize infected cells until 12 h postinfection. Additionally, we show that SIVmac239 Nef downregulated surface major histocompatibility complex class I (MHC-I) molecules beginning at 12 h postinfection, concomitant with presentation of Nef-derived CD8+ T-cell epitopes. Finally, Pol-specific CD8+ T cells eliminated infected cells as early as 6 h postinfection, well before MHC-I downregulation, suggesting a previously underappreciated antiviral role for Pol-specific CD8+ T cells.
Sacha
Jonah B
JB
Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, 555 Science Drive, Madison, WI 53711, USA.
Chung
Chungwon
C
Reed
Jason
J
Jonas
Anna K
AK
Bean
Alexander T
AT
Spencer
Sean P
SP
Lee
Wonhee
W
Vojnov
Lara
L
Rudersdorf
Richard
R
Friedrich
Thomas C
TC
Wilson
Nancy A
NA
Lifson
Jeffrey D
JD
Watkins
David I
DI
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000821:virology*; D002478:Cells, Cultured; D015536:Down-Regulation; D000939:Epitopes / Q000737:chemistry; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry; D015967:Gene Expression Regulation, Viral; D015684:Gene Products, pol / Q000378:metabolism / Q000502:physiology*; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D008253:Macaca mulatta; D008285:Major Histocompatibility Complex; D016097:Simian Acquired Immunodeficiency Syndrome / Q000378:metabolism*; D015302:Simian Immunodeficiency Virus / Q000378:metabolism*; D013997:Time Factors; D054334:Viral Regulatory and Accessory Proteins / Q000378:metabolism*
D000939:Epitopes; D018984:Epitopes, T-Lymphocyte; D015684:Gene Products, pol; D015395:Histocompatibility Antigens Class I; C429284:NEF protein, SIV; D054334:Viral Regulatory and Accessory Proteins
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