Robust, vaccine-induced CD8(+) T lymphocyte response against an out-of-frame epitope.
Rational vaccines designed to engender T cell responses require intimate knowledge of how epitopes are generated and presented. Recently, we vaccinated 8 Mamu-A*02(+) rhesus macaques with every SIV protein except Envelope (Env). Surprisingly, one of the strongest T cell responses engendered was against the Env protein, the Mamu-A*02-restricted epitope, Env(788-795)RY8. In this paper, we show that translation from an alternate reading frame of both the Rev-encoding DNA plasmid and the rAd5 vector engendered Env(788-795)RY8-specific CD8(+) T cells of greater magnitude than "normal" SIV infection. Our data demonstrate both that the pathway from vaccination to immune response is not well understood and that products of alternate reading frames may be rich and untapped sources of T cell epitopes.
Maness
Nicholas J
NJ
Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, WI 53706, USA.
Wilson
Nancy A
NA
Reed
Jason S
JS
Piaskowski
Shari M
SM
Sacha
Jonah B
JB
Walsh
Andrew D
AD
Thoryk
Elizabeth
E
Heidecker
Gwendolyn J
GJ
Citron
Michael P
MP
Liang
Xiaoping
X
Bett
Andrew J
AJ
Casimiro
Danilo R
DR
Watkins
David I
DI
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology*; D015686:Gene Products, env / Q000235:genetics / Q000276:immunology; D008253:Macaca mulatta; D008969:Molecular Sequence Data; D016364:Reading Frames / Q000235:genetics* / Q000276:immunology; D018449:SAIDS Vaccines / Q000235:genetics / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000276:immunology; D014162:Transfection; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology
D018984:Epitopes, T-Lymphocyte; D015686:Gene Products, env; D018449:SAIDS Vaccines; D014759:Viral Envelope Proteins