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PMID: 17312117 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Gag-specific CD8+ T lymphocytes recognize infected cells before AIDS-virus integration and viral protein expression.

Journal of immunology (Baltimore, Md. : 1950) ·Vol. 178 ·No. 5 ·2007-03-01 ·Pages 2746-54

Sacha JB, Chung C, Rakasz EG, Spencer SP, Jonas AK, Bean AT, Lee W, Burwitz BJ, Stephany JJ, Loffredo JT, Allison DB, Adnan S, Hoji A, Wilson NA, Friedrich TC, Lifson JD, Yang OO, Watkins DI

Abstract

CD8(+) T cells are a key focus of vaccine development efforts for HIV. However, there is no clear consensus as to which of the nine HIV proteins should be used for vaccination. The early proteins Tat, Rev, and Nef may be better CD8(+) T cell targets than the late-expressed structural proteins Gag, Pol, and Env. In this study, we show that Gag-specific CD8(+) T cells recognize infected CD4(+) T lymphocytes as early as 2 h postinfection, before proviral DNA integration, viral protein synthesis, and Nef-mediated MHC class I down-regulation. Additionally, the number of Gag epitopes recognized by CD8(+) T cells was significantly associated with lower viremia (p = 0.0017) in SIV-infected rhesus macaques. These results suggest that HIV vaccines should focus CD8(+) T cell responses on Gag.

MeSH Terms
AIDS Vaccines/immunology Acquired Immunodeficiency Syndrome/immunology,metabolism Animals CD4-Positive T-Lymphocytes/immunology,metabolism,virology CD8-Positive T-Lymphocytes/immunology,metabolism Epitopes, T-Lymphocyte/immunology,metabolism Gene Expression Regulation, Viral/immunology Gene Products, gag/immunology HIV-1/immunology Histocompatibility Antigens Class I/biosynthesis,immunology Macaca mulatta Simian Immunodeficiency Virus/immunology Time Factors Virus Integration/immunology
Chemicals
AIDS Vaccines Epitopes, T-Lymphocyte Gene Products, gag Histocompatibility Antigens Class I
Authors & Affiliations
18 authors, click to expand affiliations / ORCID
Sacha Jonah B
Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI 53711, USA.
Chung Chungwon
Rakasz Eva G
Spencer Sean P
Jonas Anna K
Bean Alexander T
Lee Wonhee
Burwitz Benjamin J
Stephany Jason J
Loffredo John T
Allison David B
Adnan Sama
Hoji Akihiko
Wilson Nancy A
Friedrich Thomas C
Lifson Jeffrey D
Yang Otto O
Watkins David I
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Article Info
Journal
Journal of immunology (Baltimore, Md. : 1950)
Abbr.
J Immunol
ISSN
0022-1767
DOI
10.4049/jimmunol.178.5.2746
Published
2007-03-01
Pages
2746-54
Language
English
Region
United States
NLM ID
2985117R
PMCID
PMC4520734
Subset
IM
Grants
NCRR NIH HHS · C06 RR020141 · United States
NCRR NIH HHS · C06 RR015459 · United States
NCRR NIH HHS · P51 RR000167 · United States
NIAID NIH HHS · R01 AI052056 · United States
NIAID NIH HHS · R37 AI052056 · United States
NCRR NIH HHS · RR 15459-01 · United States
NCRR NIH HHS · P51 RR000167-43 · United States
NCRR NIH HHS · P51 RR 000167 · United States
NCRR NIH HHS · RR 020141-01 · United States
NIAID NIH HHS · R01 AI 049120 · United States
NIAID NIH HHS · R37 AI052056-07 · United States
NIAID NIH HHS · R01 AI049120 · United States
NIAID NIH HHS · R01 AI 052056 · United States
NCRR NIH HHS · C06 RR015459-01 · United States
NCI NIH HHS · N01 CO012400 · United States
NIAID NIH HHS · R01 AI049120-07 · United States
NCI NIH HHS · N01CO12400 · United States
External Links
PubMed source DOI: 10.4049/jimmunol.178.5.2746 PMC Full Text View journal details
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