Early HLA-B*57-restricted CD8+T lymphocyte responses predict HIV-1 disease progression

Catherine A. Brennan, F. Javier Ibarrondo, Catherine A. Sugar, Mary Ann Hausner, Roger Shih, Hwee L. Ng, Roger Detels, Joseph Bernard Margolick, Charles R. Rinaldo, John Phair, Lisa Paula Jacobson, Otto O. Yang, Beth D. Jamieson

Research output: Contribution to journalArticle

Abstract

Although HLA-B*57 (B57) is associated with slow progression to disease following HIV-1 infection, B57 heterozygotes display a wide spectrum of outcomes, including rapid progression, viremic slow progression, and elite control. Efforts to identify differences between B57-positive (B57+) slow progressors and B57+ rapid progressors have largely focused on cytotoxic T lymphocyte (CTL) phenotypes and specificities during chronic stages of infection. Although CTL responses in the early months of infection are likely to be the most important for the long-term rate of HIV-1 disease progression, few data on the early CTL responses of eventual slow progressors have been available. Utilizing the Multicenter AIDS Cohort Study (MACS), we retrospectively examined the early HIV-1-specific CTL responses of 14 B57+ individuals whose time to development of disease ranged from 3.5 years to longer than 25 years after infection. In general, a greater breadth of targeting of epitopes from structural proteins, especially Gag, as well as of highly conserved epitopes from any HIV-1 protein, correlated with longer times until disease. The single elite controller in the cohort was an outlier on several correlations of CTL targeting and time until disease, consistent with reports that elite control is typically not achieved solely by protective HLA-mediated CTLs. When targeting of individual epitopes was analyzed, we found that early CTL responses to the IW9 (ISPRTLNAW) epitope of Gag, while generally subdominant, correlated with delayed progression to disease. This is the first study to identify early CTL responses to IW9 as a correlate of protection in persons with HLA-B*57.

Original languageEnglish (US)
Pages (from-to)10505-10516
Number of pages12
JournalJournal of Virology
Volume86
Issue number19
DOIs
StatePublished - Oct 2012

Fingerprint

cytotoxic T-lymphocytes
Cytotoxic T-Lymphocytes
Human immunodeficiency virus 1
disease course
Disease Progression
HIV-1
T-lymphocytes
T-Lymphocytes
epitopes
Epitopes
infection
Infection
Human Immunodeficiency Virus Proteins
gag Gene Products
structural proteins
Heterozygote
HLA-B57 antigen
cohort studies
HIV Infections
heterozygosity

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

Brennan, C. A., Javier Ibarrondo, F., Sugar, C. A., Hausner, M. A., Shih, R., Ng, H. L., ... Jamieson, B. D. (2012). Early HLA-B*57-restricted CD8+T lymphocyte responses predict HIV-1 disease progression. Journal of Virology, 86(19), 10505-10516. https://doi.org/10.1128/JVI.00102-12

Early HLA-B*57-restricted CD8+T lymphocyte responses predict HIV-1 disease progression. / Brennan, Catherine A.; Javier Ibarrondo, F.; Sugar, Catherine A.; Hausner, Mary Ann; Shih, Roger; Ng, Hwee L.; Detels, Roger; Margolick, Joseph Bernard; Rinaldo, Charles R.; Phair, John; Jacobson, Lisa Paula; Yang, Otto O.; Jamieson, Beth D.

In: Journal of Virology, Vol. 86, No. 19, 10.2012, p. 10505-10516.

Research output: Contribution to journalArticle

Brennan, CA, Javier Ibarrondo, F, Sugar, CA, Hausner, MA, Shih, R, Ng, HL, Detels, R, Margolick, JB, Rinaldo, CR, Phair, J, Jacobson, LP, Yang, OO & Jamieson, BD 2012, 'Early HLA-B*57-restricted CD8+T lymphocyte responses predict HIV-1 disease progression', Journal of Virology, vol. 86, no. 19, pp. 10505-10516. https://doi.org/10.1128/JVI.00102-12
Brennan CA, Javier Ibarrondo F, Sugar CA, Hausner MA, Shih R, Ng HL et al. Early HLA-B*57-restricted CD8+T lymphocyte responses predict HIV-1 disease progression. Journal of Virology. 2012 Oct;86(19):10505-10516. https://doi.org/10.1128/JVI.00102-12
Brennan, Catherine A. ; Javier Ibarrondo, F. ; Sugar, Catherine A. ; Hausner, Mary Ann ; Shih, Roger ; Ng, Hwee L. ; Detels, Roger ; Margolick, Joseph Bernard ; Rinaldo, Charles R. ; Phair, John ; Jacobson, Lisa Paula ; Yang, Otto O. ; Jamieson, Beth D. / Early HLA-B*57-restricted CD8+T lymphocyte responses predict HIV-1 disease progression. In: Journal of Virology. 2012 ; Vol. 86, No. 19. pp. 10505-10516.
@article{d88d2d253832407bb356a211fe0622c8,
title = "Early HLA-B*57-restricted CD8+T lymphocyte responses predict HIV-1 disease progression",
abstract = "Although HLA-B*57 (B57) is associated with slow progression to disease following HIV-1 infection, B57 heterozygotes display a wide spectrum of outcomes, including rapid progression, viremic slow progression, and elite control. Efforts to identify differences between B57-positive (B57+) slow progressors and B57+ rapid progressors have largely focused on cytotoxic T lymphocyte (CTL) phenotypes and specificities during chronic stages of infection. Although CTL responses in the early months of infection are likely to be the most important for the long-term rate of HIV-1 disease progression, few data on the early CTL responses of eventual slow progressors have been available. Utilizing the Multicenter AIDS Cohort Study (MACS), we retrospectively examined the early HIV-1-specific CTL responses of 14 B57+ individuals whose time to development of disease ranged from 3.5 years to longer than 25 years after infection. In general, a greater breadth of targeting of epitopes from structural proteins, especially Gag, as well as of highly conserved epitopes from any HIV-1 protein, correlated with longer times until disease. The single elite controller in the cohort was an outlier on several correlations of CTL targeting and time until disease, consistent with reports that elite control is typically not achieved solely by protective HLA-mediated CTLs. When targeting of individual epitopes was analyzed, we found that early CTL responses to the IW9 (ISPRTLNAW) epitope of Gag, while generally subdominant, correlated with delayed progression to disease. This is the first study to identify early CTL responses to IW9 as a correlate of protection in persons with HLA-B*57.",
author = "Brennan, {Catherine A.} and {Javier Ibarrondo}, F. and Sugar, {Catherine A.} and Hausner, {Mary Ann} and Roger Shih and Ng, {Hwee L.} and Roger Detels and Margolick, {Joseph Bernard} and Rinaldo, {Charles R.} and John Phair and Jacobson, {Lisa Paula} and Yang, {Otto O.} and Jamieson, {Beth D.}",
year = "2012",
month = "10",
doi = "10.1128/JVI.00102-12",
language = "English (US)",
volume = "86",
pages = "10505--10516",
journal = "Journal of Virology",
issn = "0022-538X",
publisher = "American Society for Microbiology",
number = "19",

}

TY - JOUR

T1 - Early HLA-B*57-restricted CD8+T lymphocyte responses predict HIV-1 disease progression

AU - Brennan, Catherine A.

AU - Javier Ibarrondo, F.

AU - Sugar, Catherine A.

AU - Hausner, Mary Ann

AU - Shih, Roger

AU - Ng, Hwee L.

AU - Detels, Roger

AU - Margolick, Joseph Bernard

AU - Rinaldo, Charles R.

AU - Phair, John

AU - Jacobson, Lisa Paula

AU - Yang, Otto O.

AU - Jamieson, Beth D.

PY - 2012/10

Y1 - 2012/10

N2 - Although HLA-B*57 (B57) is associated with slow progression to disease following HIV-1 infection, B57 heterozygotes display a wide spectrum of outcomes, including rapid progression, viremic slow progression, and elite control. Efforts to identify differences between B57-positive (B57+) slow progressors and B57+ rapid progressors have largely focused on cytotoxic T lymphocyte (CTL) phenotypes and specificities during chronic stages of infection. Although CTL responses in the early months of infection are likely to be the most important for the long-term rate of HIV-1 disease progression, few data on the early CTL responses of eventual slow progressors have been available. Utilizing the Multicenter AIDS Cohort Study (MACS), we retrospectively examined the early HIV-1-specific CTL responses of 14 B57+ individuals whose time to development of disease ranged from 3.5 years to longer than 25 years after infection. In general, a greater breadth of targeting of epitopes from structural proteins, especially Gag, as well as of highly conserved epitopes from any HIV-1 protein, correlated with longer times until disease. The single elite controller in the cohort was an outlier on several correlations of CTL targeting and time until disease, consistent with reports that elite control is typically not achieved solely by protective HLA-mediated CTLs. When targeting of individual epitopes was analyzed, we found that early CTL responses to the IW9 (ISPRTLNAW) epitope of Gag, while generally subdominant, correlated with delayed progression to disease. This is the first study to identify early CTL responses to IW9 as a correlate of protection in persons with HLA-B*57.

AB - Although HLA-B*57 (B57) is associated with slow progression to disease following HIV-1 infection, B57 heterozygotes display a wide spectrum of outcomes, including rapid progression, viremic slow progression, and elite control. Efforts to identify differences between B57-positive (B57+) slow progressors and B57+ rapid progressors have largely focused on cytotoxic T lymphocyte (CTL) phenotypes and specificities during chronic stages of infection. Although CTL responses in the early months of infection are likely to be the most important for the long-term rate of HIV-1 disease progression, few data on the early CTL responses of eventual slow progressors have been available. Utilizing the Multicenter AIDS Cohort Study (MACS), we retrospectively examined the early HIV-1-specific CTL responses of 14 B57+ individuals whose time to development of disease ranged from 3.5 years to longer than 25 years after infection. In general, a greater breadth of targeting of epitopes from structural proteins, especially Gag, as well as of highly conserved epitopes from any HIV-1 protein, correlated with longer times until disease. The single elite controller in the cohort was an outlier on several correlations of CTL targeting and time until disease, consistent with reports that elite control is typically not achieved solely by protective HLA-mediated CTLs. When targeting of individual epitopes was analyzed, we found that early CTL responses to the IW9 (ISPRTLNAW) epitope of Gag, while generally subdominant, correlated with delayed progression to disease. This is the first study to identify early CTL responses to IW9 as a correlate of protection in persons with HLA-B*57.

UR - http://www.scopus.com/inward/record.url?scp=84868675469&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84868675469&partnerID=8YFLogxK

U2 - 10.1128/JVI.00102-12

DO - 10.1128/JVI.00102-12

M3 - Article

C2 - 22811521

AN - SCOPUS:84868675469

VL - 86

SP - 10505

EP - 10516

JO - Journal of Virology

JF - Journal of Virology

SN - 0022-538X

IS - 19

ER -