Patient-Specific Cytotoxic T-Lymphocyte Cross-Recognition of Naturally Occurring Variants of a Human Immunodeficiency Virus Type 1 (HIV-1) p24<sup><i>gag</i></sup>Epitope by HIV-1-Infected Children

Buseyne, Florence; Chaix, Marie Laure; Rouzioux, C.; Blanche, Stéphane; Rivière, Yves

doi:10.1128/jvi.75.10.4941-4946.2001

Cited by 12 publications

(13 citation statements)

References 25 publications

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“…The efficient cross-reactivity of T cells specific for the B58-restricted gag 241-50 epitope in HIV-2 extends the data from a previous study in HIV-2-infected patients, the majority of whom had gagspecific CTL lines capable of cross-recognizing HIV-1 gag, with some having lytic responses to the gag 240 -252 region on peptide mapping (38). We observed some variability between individuals in the amount of cross-recognition as suggested from previous studies (38,39). Although the differences we identified may have a degree of epitope selectivity (40,41), the global molecular analysis points to an overall reduction in large oligoclonal expansions in the total virus-specific response to HIV-2 compared with HIV-1 infection.…”

Section: Discussionsupporting

confidence: 79%

Greater CD8+ TCR Heterogeneity and Functional Flexibility in HIV-2 Compared to HIV-1 Infection

Lopes

Jaye

Dorrell

et al. 2003

The Journal of Immunology

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Virus-specific CD8+ T cells are known to play an important role in the control of HIV infection. In this study we investigated whether there may be qualitative differences in the CD8+ T cell response in HIV-1- and HIV-2-infected individuals that contribute to the relatively efficient control of the latter infection. A molecular comparison of global TCR heterogeneity showed a more oligoclonal pattern of CD8 cells in HIV-1- than HIV-2-infected patients. This was reflected in restricted and conserved TCR usage by CD8+ T cells recognizing individual HLA-A2- and HLA-B57-restricted viral epitopes in HIV-1, with limited plasticity in their response to amino acid substitutions within these epitopes. The more diverse TCR usage observed for HIV-2-specific CD8+ T cells was associated with an enhanced potential for CD8 expansion and IFN-γ production on cross-recognition of variant epitopes. Our data suggest a mechanism that could account for any possible cross-protection that may be mediated by HIV-2-specific CD8+ T cells against HIV-1 infection. Furthermore, they have implications for HIV vaccine development, demonstrating an association between a polyclonal, virus-specific CD8+ T cell response and an enhanced capacity to tolerate substitutions within T cell epitopes.

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Section: Discussionsupporting

confidence: 79%

Greater CD8+ TCR Heterogeneity and Functional Flexibility in HIV-2 Compared to HIV-1 Infection

Lopes

Jaye

Dorrell

et al. 2003

The Journal of Immunology

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“…Thus, also stimulation with A/Victoria/3/75 (H3N2) led to the expansion of NP DSI -specific cells cross-reactive with NP DTI . This finding resembles the cross-reactivity observed with CTL specific for epitopes in HIV-1, dengue virus, and SIV (33)(34)(35). HIV-1-specific CTL could recognize variants of epitopes present in different clades of this virus.…”

Section: Discussionsupporting

confidence: 52%

Recognition of Homo- and Heterosubtypic Variants of Influenza A Viruses by Human CD8+ T Lymphocytes

Boon

Mutsert

Baarle

et al. 2004

The Journal of Immunology

114

105

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In the present study, the recognition of epitope variants of influenza A viruses by human CTL was investigated. To this end, human CD8+ CTL clones, specific for natural variants of the HLA-B*3501-restricted epitope in the nucleoprotein (NP418–426), were generated. As determined in 51Cr release assays and by flow cytometry with HLA-B*3501-peptide tetrameric complexes, CTL clones were found to be specific for epitopes within one subtype or cross-reactive with heterosubtypic variants of the epitope. Using eight natural variants of the epitope, positions in the 9-mer important for T cell recognition and involved in escape from CTL immunity were identified and visualized using multidimensional scaling. It was shown that positions 4 and 5 in the 9-mer epitope were important determinants of T cell specificity. The in vivo existence of CD8+ cells cross-reactive with homo- and heterosubtypic variants of the epitope was further confirmed using polyclonal T cell populations obtained after stimulation of PBMC with different influenza A viruses. Based on the observed recognition patterns of the clonal and polyclonal T cell populations and serology, it is hypothesized that consecutive infections with influenza viruses containing different variants of the epitope select for cross-reactive T cells in vivo.

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“…There is increasing evidence that both CD4 ϩ and CD8 ϩ subsets are probably required for strong CTL memory and protection against HIV-1 (51, 55, 58). HIV-1 Gag is one of the most conserved viral proteins, and broad, cross-clade CTL responses recognizing conserved epitopes in HIV-1 Gag have been detected in HIV-1-infected individuals (5,8,23). Therefore, the induction of CTL and T-helper responses against conserved Gag epitopes via fusogenic HIV-1 or heterologous envelope-mediated targeting of Gag particles to APC in vivo could be significant for the development of a safe and effective HIV-1 DNA vaccine.…”

Section: Fig 5 Cd4mentioning

confidence: 99%

“…It was constructed by inverting a BamHI-BamHI fragment encompassing the VSV-G gene in pCMV-VSV. Plasmid pCMV-VSV mut encodes a fusion-defective VSV-G protein (mutant Q117N) (8,70).…”

Section: Hiv-1 Gag and Vsv-g Expression Vectorsmentioning

confidence: 99%

Enhanced Presentation of Major Histocompatibility Complex Class I-Restricted Human Immunodeficiency Virus Type 1 (HIV-1) Gag-Specific Epitopes after DNA Immunization with Vectors Coding for Vesicular Stomatitis Virus Glycoprotein- Pseudotyped HIV-1 Gag Particles

Marsac

Loirat

Petit

et al. 2002

J Virol

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In vivo priming of cytotoxic T lymphocytes (CTL) by DNA injection predominantly occurs by antigen transfer from DNA-transfected cells to antigen-presenting cells. A rational strategy for increasing DNA vaccine potency would be to use a delivery system that facilitates antigen uptake by antigen-presenting cells. Exogenous antigen presentation through the major histocompatibility complex (MHC) class I-restricted pathway of some viral antigens is increased after adequate virus-receptor interaction and the fusion of viral and cellular membranes. We used DNA-based immunization with plasmids coding for human immunodeficiency virus type 1 (HIV-1) Gag particles pseudotyped with vesicular stomatitis virus glycoprotein (VSV-G) to generate Gag-specific CTL responses. The presence of the VSV-G-encoding plasmid not only increased the number of mice displaying anti-Gag-specific cytotoxic response but also increased the efficiency of specific lysis. In vitro analysis of processing confirmed that exogenous presentation of Gag epitopes occurred much more efficiently when Gag particles were pseudotyped with the VSV-G envelope. We show that the VSV-G-pseudotyped Gag particles not only entered the MHC class II processing pathway but also entered the MHC class I processing pathway. In contrast, naked Gag particles entered the MHC class II processing pathway only. Thus, the combined use of DNA-based immunization and nonreplicating pseudotyped virus to deliver HIV-1 antigen to the immune system in vivo could be considered in HIV-1 vaccine design.

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Patient-Specific Cytotoxic T-Lymphocyte Cross-Recognition of Naturally Occurring Variants of a Human Immunodeficiency Virus Type 1 (HIV-1) p24^gagEpitope by HIV-1-Infected Children

Cited by 12 publications

References 25 publications

Greater CD8+ TCR Heterogeneity and Functional Flexibility in HIV-2 Compared to HIV-1 Infection

Greater CD8+ TCR Heterogeneity and Functional Flexibility in HIV-2 Compared to HIV-1 Infection

Recognition of Homo- and Heterosubtypic Variants of Influenza A Viruses by Human CD8+ T Lymphocytes

Enhanced Presentation of Major Histocompatibility Complex Class I-Restricted Human Immunodeficiency Virus Type 1 (HIV-1) Gag-Specific Epitopes after DNA Immunization with Vectors Coding for Vesicular Stomatitis Virus Glycoprotein- Pseudotyped HIV-1 Gag Particles

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Patient-Specific Cytotoxic T-Lymphocyte Cross-Recognition of Naturally Occurring Variants of a Human Immunodeficiency Virus Type 1 (HIV-1) p24gagEpitope by HIV-1-Infected Children

Cited by 12 publications

References 25 publications

Greater CD8+ TCR Heterogeneity and Functional Flexibility in HIV-2 Compared to HIV-1 Infection

Greater CD8+ TCR Heterogeneity and Functional Flexibility in HIV-2 Compared to HIV-1 Infection

Recognition of Homo- and Heterosubtypic Variants of Influenza A Viruses by Human CD8+ T Lymphocytes

Enhanced Presentation of Major Histocompatibility Complex Class I-Restricted Human Immunodeficiency Virus Type 1 (HIV-1) Gag-Specific Epitopes after DNA Immunization with Vectors Coding for Vesicular Stomatitis Virus Glycoprotein- Pseudotyped HIV-1 Gag Particles

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Patient-Specific Cytotoxic T-Lymphocyte Cross-Recognition of Naturally Occurring Variants of a Human Immunodeficiency Virus Type 1 (HIV-1) p24^gagEpitope by HIV-1-Infected Children