Comprehensive Analysis of Human Immunodeficiency Virus Type 1 (HIV-1)-Specific Gamma Interferon-Secreting CD8+ T Cells in Primary HIV-1 Infection

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Published inJournal of Virology Vol. 77; no. 12; pp. 6867 - 6878
Main Authors Cao, Jianhong, McNevin, John, Holte, Sarah, Fink, Lisa, Corey, Lawrence, McElrath, M. Juliana
Format Journal Article
LanguageEnglish
Published United States American Society for Microbiology 01.06.2003
Subjects
Acute Disease
Adult
Amino Acid Sequence
CD8-Positive T-Lymphocytes - immunology
CD8-Positive T-Lymphocytes - metabolism
Epitope Mapping
Epitopes, T-Lymphocyte - immunology
Histocompatibility Antigens Class I - metabolism
HIV Infections - immunology
HIV Infections - virology
HIV-1 - immunology
Humans
Interferon-gamma - metabolism
Male
Molecular Sequence Data
Pathogenesis and Immunity
Viral Load
Viral Proteins - chemistry
Viral Proteins - metabolism
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Abstract Article Usage Stats Services JVI Citing Articles Google Scholar PubMed Related Content Social Bookmarking CiteULike Delicious Digg Facebook Google+ Mendeley Reddit StumbleUpon Twitter current issue Spotlights in the Current Issue JVI About JVI Subscribers Authors Reviewers Advertisers Inquiries from the Press Permissions & Commercial Reprints ASM Journals Public Access Policy JVI RSS Feeds 1752 N Street N.W. • Washington DC 20036 202.737.3600 • 202.942.9355 fax • journals@asmusa.org Print ISSN: 0022-538X Online ISSN: 1098-5514 Copyright © 2014 by the American Society for Microbiology.   For an alternate route to JVI .asm.org, visit: JVI       
AbstractList Human immunodeficiency virus type 1 (HIV-1)-specific CD8 + T cells provide an important defense in controlling HIV-1 replication, particularly following acquisition of infection. To delineate the breadth and potency of these responses in patients upon initial presentation and before treatment, we determined the fine specificities and frequencies of gamma interferon (IFN-γ)-secreting CD8 + T cells recognizing all HIV-1 proteins in patients with primary infection. In these subjects, the earliest detected responses were directed predominantly against Nef, Tat, Vpr, and Env. Tat- and Vpr-specific CD8 + T cells accounted for the greatest frequencies of mean IFN-γ spot-forming cells (SFC). Nef-specific responses (10 of 21) were more commonly detected. A mean of 2.3 epitopes were recognized with various avidities per subject, and the number increased with the duration of infection ( R = 0.47, P = 0.031). The mean frequency of CD8 + T cells (985 SFC/10 6 peripheral blood mononuclear cells) correlated with the number of epitopes recognized ( R = 0.84, P < 0.0001) and the number of HLA-restricting alleles ( R = 0.79, P < 0.0001). Neither the total SFC frequencies nor the number of epitopes recognized correlated with the concurrent plasma viral load. Seventeen novel epitopes were identified, four of which were restricted to HLA alleles (A23 and B72) that are common among African descendents. Thus, primary HIV-1 infection induces strong CD8 + -T-cell immunity whose specificities broaden over time, but their frequencies and breadth do not correlate with HIV-1 containment when examined concurrently. Many novel epitopes, particularly directed to Nef, Tat, and Env, and frequently with unique HLA restrictions, merit further consideration in vaccine design.
Human immunodeficiency virus type 1 (HIV-1)-specific CD8(+) T cells provide an important defense in controlling HIV-1 replication, particularly following acquisition of infection. To delineate the breadth and potency of these responses in patients upon initial presentation and before treatment, we determined the fine specificities and frequencies of gamma interferon (IFN-gamma)-secreting CD8(+) T cells recognizing all HIV-1 proteins in patients with primary infection. In these subjects, the earliest detected responses were directed predominantly against Nef, Tat, Vpr, and Env. Tat- and Vpr-specific CD8(+) T cells accounted for the greatest frequencies of mean IFN-gamma spot-forming cells (SFC). Nef-specific responses (10 of 21) were more commonly detected. A mean of 2.3 epitopes were recognized with various avidities per subject, and the number increased with the duration of infection (R = 0.47, P = 0.031). The mean frequency of CD8(+) T cells (985 SFC/10(6) peripheral blood mononuclear cells) correlated with the number of epitopes recognized (R = 0.84, P < 0.0001) and the number of HLA-restricting alleles (R = 0.79, P < 0.0001). Neither the total SFC frequencies nor the number of epitopes recognized correlated with the concurrent plasma viral load. Seventeen novel epitopes were identified, four of which were restricted to HLA alleles (A23 and B72) that are common among African descendents. Thus, primary HIV-1 infection induces strong CD8(+)-T-cell immunity whose specificities broaden over time, but their frequencies and breadth do not correlate with HIV-1 containment when examined concurrently. Many novel epitopes, particularly directed to Nef, Tat, and Env, and frequently with unique HLA restrictions, merit further consideration in vaccine design.
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Human immunodeficiency virus type 1 (HIV-1)-specific CD8(+) T cells provide an important defense in controlling HIV-1 replication, particularly following acquisition of infection. To delineate the breadth and potency of these responses in patients upon initial presentation and before treatment, we determined the fine specificities and frequencies of gamma interferon (IFN-gamma)-secreting CD8(+) T cells recognizing all HIV-1 proteins in patients with primary infection. In these subjects, the earliest detected responses were directed predominantly against Nef, Tat, Vpr, and Env. Tat- and Vpr-specific CD8(+) T cells accounted for the greatest frequencies of mean IFN-gamma spot-forming cells (SFC). Nef-specific responses (10 of 21) were more commonly detected. A mean of 2.3 epitopes were recognized with various avidities per subject, and the number increased with the duration of infection (R = 0.47, P = 0.031). The mean frequency of CD8(+) T cells (985 SFC/10(6) peripheral blood mononuclear cells) correlated with the number of epitopes recognized (R = 0.84, P < 0.0001) and the number of HLA-restricting alleles (R = 0.79, P < 0.0001). Neither the total SFC frequencies nor the number of epitopes recognized correlated with the concurrent plasma viral load. Seventeen novel epitopes were identified, four of which were restricted to HLA alleles (A23 and B72) that are common among African descendents. Thus, primary HIV-1 infection induces strong CD8(+)-T-cell immunity whose specificities broaden over time, but their frequencies and breadth do not correlate with HIV-1 containment when examined concurrently. Many novel epitopes, particularly directed to Nef, Tat, and Env, and frequently with unique HLA restrictions, merit further consideration in vaccine design.Human immunodeficiency virus type 1 (HIV-1)-specific CD8(+) T cells provide an important defense in controlling HIV-1 replication, particularly following acquisition of infection. To delineate the breadth and potency of these responses in patients upon initial presentation and before treatment, we determined the fine specificities and frequencies of gamma interferon (IFN-gamma)-secreting CD8(+) T cells recognizing all HIV-1 proteins in patients with primary infection. In these subjects, the earliest detected responses were directed predominantly against Nef, Tat, Vpr, and Env. Tat- and Vpr-specific CD8(+) T cells accounted for the greatest frequencies of mean IFN-gamma spot-forming cells (SFC). Nef-specific responses (10 of 21) were more commonly detected. A mean of 2.3 epitopes were recognized with various avidities per subject, and the number increased with the duration of infection (R = 0.47, P = 0.031). The mean frequency of CD8(+) T cells (985 SFC/10(6) peripheral blood mononuclear cells) correlated with the number of epitopes recognized (R = 0.84, P < 0.0001) and the number of HLA-restricting alleles (R = 0.79, P < 0.0001). Neither the total SFC frequencies nor the number of epitopes recognized correlated with the concurrent plasma viral load. Seventeen novel epitopes were identified, four of which were restricted to HLA alleles (A23 and B72) that are common among African descendents. Thus, primary HIV-1 infection induces strong CD8(+)-T-cell immunity whose specificities broaden over time, but their frequencies and breadth do not correlate with HIV-1 containment when examined concurrently. Many novel epitopes, particularly directed to Nef, Tat, and Env, and frequently with unique HLA restrictions, merit further consideration in vaccine design.
Author John McNevin
M. Juliana McElrath
Sarah Holte
Jianhong Cao
Lisa Fink
Lawrence Corey
AuthorAffiliation Program in Infectious Diseases, Clinical Research Division, 1 Program in Biostatistics, Public Health Science Division, Fred Hutchinson Cancer Research Center, 3 Department of Medicine, 2 Department of Laboratory Medicine, University of Washington, Seattle, Washington 4
AuthorAffiliation_xml – name: Program in Infectious Diseases, Clinical Research Division, 1 Program in Biostatistics, Public Health Science Division, Fred Hutchinson Cancer Research Center, 3 Department of Medicine, 2 Department of Laboratory Medicine, University of Washington, Seattle, Washington 4
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  organization: Program in Infectious Diseases, Clinical Research Division
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/12768006$$D View this record in MEDLINE/PubMed
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Corresponding author. Mailing address: Fred Hutchinson Cancer Research Center, D3-100, 1100 Fairview Ave. North, P.O. Box 19024, Seattle, WA 98109. Phone: (206) 667-6704. Fax: (206) 667-4411. E-mail: kd@u.washington.edu.
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Human immunodeficiency virus type 1 (HIV-1)-specific CD8 + T cells provide an important defense in controlling HIV-1 replication, particularly following...
Human immunodeficiency virus type 1 (HIV-1)-specific CD8(+) T cells provide an important defense in controlling HIV-1 replication, particularly following...
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SubjectTerms Acute Disease
Adult
Amino Acid Sequence
CD8-Positive T-Lymphocytes - immunology
CD8-Positive T-Lymphocytes - metabolism
Epitope Mapping
Epitopes, T-Lymphocyte - immunology
Histocompatibility Antigens Class I - metabolism
HIV Infections - immunology
HIV Infections - virology
HIV-1 - immunology
Humans
Interferon-gamma - metabolism
Male
Molecular Sequence Data
Pathogenesis and Immunity
Viral Load
Viral Proteins - chemistry
Viral Proteins - metabolism
Title Comprehensive Analysis of Human Immunodeficiency Virus Type 1 (HIV-1)-Specific Gamma Interferon-Secreting CD8+ T Cells in Primary HIV-1 Infection
URI http://jvi.asm.org/content/77/12/6867.abstract
https://www.ncbi.nlm.nih.gov/pubmed/12768006
https://www.proquest.com/docview/73304002
https://pubmed.ncbi.nlm.nih.gov/PMC156203
Volume 77
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