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PMID: 11148222 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Substantial differences in specificity of HIV-specific cytotoxic T cells in acute and chronic HIV infection.

The Journal of experimental medicine ·Vol. 193 ·No. 2 ·2001-01-15 ·Pages 181-94

Goulder PJ, Altfeld MA, Rosenberg ES, Nguyen T, Tang Y, Eldridge RL, Addo MM, He S, Mukherjee JS, Phillips MN, Bunce M, Kalams SA, Sekaly RP, Walker BD, Brander C

Abstract

Cytotoxic T lymphocytes (CTLs) play a vital part in controlling viral replication during human viral infections. Most studies in human infections have focused on CTL specificities in chronic infection and few data exist regarding the specificity of the initial CTL response induced in acute infection. In this study, HIV-1 infection in persons expressing human histocompatibility leukocyte antigen (HLA)-A*0201 was used as a means of addressing this issue. In chronic infection, the dominant HLA-A*0201-restricted CTL response is directed towards the epitope SLYNTVATL ("SL9") in p17 Gag (residues 77-85). This epitope is targeted by 75% of HLA-A*0201-positive adults, and the magnitude of this A*0201-SL9 response shows a strong negative association with viral load in progressive infection. Despite using the highly sensitive peptide-major histocompatibility complex tetramer and intracellular cytokine assays, responses to the SL9 epitope were not detectable in any of 11 HLA-A*0201-positive subjects with acute HIV-1 infection (P = 2 x 10(-6)), even when assays were repeated using the SL9 peptide variant that was encoded by their autologous virus. In contrast, multiple responses (median 3) to other epitopes were evident in 7 of the 11 A*0201-positive subjects. Longitudinal study of two subjects confirmed that the A*0201-SL9 response emerged later than other CTL responses, and after viral set point had been reached. Together, these data show that the CTL responses that are present and that even may dominate in chronic infection may differ substantially from those that constitute the initial antiviral CTL response. This finding is an important consideration in vaccine design and in the evaluation of vaccine candidates.

MeSH Terms
Acute Disease Adult Amino Acid Sequence Chronic Disease Epitopes/genetics Female Gene Products, gag/genetics,immunology Genetic Variation HIV Antigens/genetics,immunology HIV Infections/immunology HIV-1/genetics,immunology HLA-A2 Antigen Humans Male Middle Aged T-Lymphocytes, Cytotoxic/immunology Time Factors Viral Proteins gag Gene Products, Human Immunodeficiency Virus
Chemicals
Epitopes Gene Products, gag HIV Antigens HLA-A2 Antigen Viral Proteins gag Gene Products, Human Immunodeficiency Virus p17 protein, Human Immunodeficiency Virus Type 1
Authors & Affiliations
15 authors, click to expand affiliations / ORCID
Goulder P J
Partners AIDS Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts 02129, USA. goulder@helix.mgh.harvard.edu
Altfeld M A
Rosenberg E S
Nguyen T
Tang Y
Eldridge R L
Addo M M
He S
Mukherjee J S
Phillips M N
Bunce M
Kalams S A
Sekaly R P
Walker B D
Brander C
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.193.2.181
Email
goulder@helix.mgh.harvard.edu
Published
2001-01-15
Pages
181-94
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2193346
Subset
IM
Grants
NIAID NIH HHS · AI01541 · United States
NIAID NIH HHS · AI46995 · United States
NIAID NIH HHS · AI28568 · United States
External Links
PubMed source DOI: 10.1084/jem.193.2.181 PMC Full Text View journal details
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