Important contribution of p15 Gag-specific responses to the total Gag-specific CTL responses

被引:30
作者
Yu, XG
Shang, H
Addo, MM
Eldridge, RL
Phillips, MN
Feeney, ME
Strick, D
Brander, C
Goulder, PJR
Rosenberg, ES
Walker, BD
Altfeld, M
机构
[1] Massachusetts Gen Hosp, Partner AIDS Res Ctr, Boston, MA 02114 USA
[2] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA
[3] Harvard Univ, Sch Med, Boston, MA USA
[4] First Affiliated Hosp China Med Univ, AIDS Res Ctr, Shenyang, Peoples R China
[5] John Radcliffe Hosp, Nuffield Dept Med, Oxford OX3 9DU, England
关键词
HIV-1; cytotoxic T lymphocytes; CTL epitopes; Gag; p15; HLA-A*0201;
D O I
10.1097/00002030-200202150-00002
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Objectives: HIV-1 p15 Gag and its protease cleavage products, NCp7 and p6, are believed to play a major role in viral infectivity and assembly during the early and late stages of the retroviral life cycle. However, the extent to which p15 Gag is targeted by the host immune system in natural infection as well as precise cytotoxic T lymphocyte (CTL) epitopes within this protein remains to be defined. Methods: In this study, 57 HIV-1 infected individuals and 10 HIV-1 negative controls were screened for CD8 and CD4 T-cell responses using overlapping peptides spanning the entire p15 Gag protein as well as the p] 7 Gag and p24 Gag proteins. Peptide-specific interferon-gamma production was measured by Elispot assay and flow-based intracellular cytokine quantification, and cytotoxic activity was confirmed after isolation of peptide-specific CD8 T-cell lines. Results: CD8 T lymphocytes specific to p15 Gag were found in 46% (26/57) of HIV-1 infected individuals studied and contributed on average 17% (range, 0-100%) to the total Gag-specific T-cell responses. Responses were clustered within three immunodominant regions of p15 Gag, mapping to important functional sites. These studies also include the description of the first three optimally defined CTL epitopes within p15 Gag. Conclusions: These results indicate that p] 5 Gag is frequently recognized by HIV-1 specific CD8 T cells in HIV-1 infection and will be important in the comprehensive assessments of CTL responses in infected persons, as well as the design and testing of future HIV-1 vaccines and immunotherapeutic interventions. (C) 2002 Lippincott Williams Wilkins.
引用
收藏
页码:321 / 328
页数:8
相关论文
共 34 条
  • [21] Korber B, 1999, HIV MOL IMMUNOLOGY D
  • [22] Use of recombinant protein to identify a motif-negative human cytotoxic T-cell epitope presented by HLA-A2 in the hepatitis C virus NS3 region
    Kurokohchi, K
    Akatsuka, T
    Pendleton, CD
    Takamizawa, A
    Nishioka, M
    Battegay, M
    Feinstone, SM
    Berzofsky, JA
    [J]. JOURNAL OF VIROLOGY, 1996, 70 (01) : 232 - 240
  • [23] Role for HLA class II molecules in HIV-1 suppression and cellular immunity following antiretroviral treatment
    Malhotra, U
    Holte, S
    Dutta, S
    Berrey, MM
    Delpit, E
    Koelle, DM
    Sette, A
    Corey, L
    McElrath, MJ
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 2001, 107 (04) : 505 - 517
  • [24] SPATIAL PROXIMITY OF THE HIV-1 NUCLEOCAPSID PROTEIN ZINC FINGERS INVESTIGATED BY TIME-RESOLVED FLUORESCENCE AND FLUORESCENCE RESONANCE ENERGY-TRANSFER
    MELY, Y
    JULLIAN, N
    MORELLET, N
    DEROCQUIGNY, H
    DONG, CZ
    PIEMONT, E
    ROQUES, BP
    GERARD, D
    [J]. BIOCHEMISTRY, 1994, 33 (40) : 12085 - 12091
  • [25] CONFORMATIONAL BEHAVIOR OF THE ACTIVE AND INACTIVE FORMS OF THE NUCLEOCAPSID NCP7 OF HIV-1 STUDIED BY H-1-NMR
    MORELLET, N
    DEROCQUIGNY, H
    MELY, Y
    JULLIAN, N
    DEMENE, H
    OTTMANN, M
    GERARD, D
    DARLIX, JL
    FOURNIEZALUSKI, MC
    ROQUES, BP
    [J]. JOURNAL OF MOLECULAR BIOLOGY, 1994, 235 (01) : 287 - 301
  • [26] Quantitation of HIV-1-specific cytotoxic T lymphocytes and plasma load of viral RNA
    Ogg, GS
    Jin, X
    Bonhoeffer, S
    Dunbar, PR
    Nowak, MA
    Monard, S
    Segal, JP
    Cao, YZ
    Rowland-Jones, SL
    Cerundolo, V
    Hurley, A
    Markowitz, M
    Ho, DD
    Nixon, DF
    McMichael, AJ
    [J]. SCIENCE, 1998, 279 (5359) : 2103 - 2106
  • [27] Decay kinetics of human immunodeficiency virus-specific effector cytotoxic T lymphocytes after combination antiretroviral therapy
    Ogg, GS
    Jin, X
    Bonhoeffer, S
    Moss, P
    Nowak, MA
    Monard, S
    Segal, JP
    Cao, Y
    Rowland-Jones, SL
    Hurley, A
    Markowitz, M
    Ho, DD
    McMichael, AJ
    Nixon, DF
    [J]. JOURNAL OF VIROLOGY, 1999, 73 (01) : 797 - 800
  • [28] THE CENTRAL GLOBULAR DOMAIN OF THE NUCLEOCAPSID PROTEIN OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 IS CRITICAL FOR VIRION STRUCTURE AND INFECTIVITY
    OTTMANN, M
    GABUS, C
    DARLIX, JL
    [J]. JOURNAL OF VIROLOGY, 1995, 69 (03) : 1778 - 1784
  • [29] HIV-1-specific CD4+ T cells are detectable in most individuals with active HIV-1 infection, but decline with prolonged viral suppression
    Pitcher, CJ
    Quittner, C
    Peterson, DM
    Connors, M
    Koup, RA
    Maino, VC
    Picker, LJ
    [J]. NATURE MEDICINE, 1999, 5 (05) : 518 - 525
  • [30] Vigorous HIV-1-specific CD4(+) T cell responses associated with control of viremia
    Rosenberg, ES
    Billingsley, JM
    Caliendo, AM
    Boswell, SL
    Sax, PE
    Kalams, SA
    Walker, BD
    [J]. SCIENCE, 1997, 278 (5342) : 1447 - 1450