Broad Cross-Clade T-Cell Responses to Gag in Individuals Infected with Human Immunodeficiency Virus Type 1 Non-B Clades (A to G): Importance of HLA Anchor Residue Conservation

Geels, Mark J.; Dubey, Sheri; Anderson, Kelsey; Baan, Elly; Bakker, Margreet; Pollakis, Georgios; Paxton, William A.; Shiver, John W.; Goudsmit, Jaap

doi:10.1128/jvi.79.17.11247-11258.2005

Cited by 40 publications

(30 citation statements)

References 59 publications

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“…Initial reports included only subtype B-or C-infected patients (1,(47)(48)(49), but more recently other subtypes and CRF recombinant forms are being studied (18,22,27,28,35). On the other hand, the immunoprotective role of HIV-specific vaccine-induced T cells may be limited by the large genetic distance between viral strains circulating in different locations and the vaccine strain.…”

Section: Discussionmentioning

confidence: 99%

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Magnitude, Breadth, and Functional Profile of T-Cell Responses during Human Immunodeficiency Virus Primary Infection with B and BF Viral Variants

Turk

Gherardi

Laufer

et al. 2008

J Virol

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Human immunodeficiency virus type 1 (HIV-1)-specific cytotoxic T lymphocytes (CTLs) arising during the acute phase of infection are associated with containment of viral replication and resolution of acute-phase symptoms (5,13,14,44). Detailed characterization of these cell populations and viral immunodominant epitopes will provide key data for developing and enhancing immunization strategies. In this sense, one major challenge is HIV variability, characterized by substantial inter-and intraclade sequence diversity. To date, most reports aimed at studying CTL responses are focused on HIV clade Band C-infected patients. In Argentina, epidemiological studies revealed that early predominance of B subtype has been overshadowed by the emergence of BF recombinants (16,23,32,33,53). These reports indicate that near 50% of the HIVinfected people living in Argentina are infected either with the circulating recombinant form CRF12_BF or other BF recombinant forms related to CRF12_BF. Moreover, in other South American countries, such as Brazil and Uruguay, high prevalence of F subtype and BF recombinant variants are also found (16,32,34). These findings provide an adequate scenario to fill the gap concerning fine mapping of CTL responses in nonclade B-and C-infected patients.Cross-clade CTL responses were studied by different groups using different approaches. The first publications used vaccinia virus-based constructs or peptide pools as stimulating factors (2,19,20,27). Not until recently was fine mapping of these responses achieved by using individual peptides based on different subtypes (22,28). The latter allows for a more detailed and comprehensive understanding of cross-clade reactive populations.Here, cross-clade and clade-specific T-cell responses in Band BF-infected patients from Argentina are reported. These assays were performed shortly after seroconversion in order to avoid the confounders associated with viral diversification, selection of escape mutants, and superinfection. Overlapping peptides spanning the Nef protein were chosen as antigens because of the following: (i) Nef is halfway along the spectrum of variability found in HIV proteins; (ii) during primary HIV infection, Nef-specific CTLs represent between 46% and 94% of the total magnitude of the HIV T-cell response (43); (iii) Nef has, together with Gag, the highest epitope density (1,39). This study also contributes to minimizing the problem of breadth underestimation during CTL screening and provides insights into discrepancies of CD8 T-cell effector function.

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Section: Discussionmentioning

confidence: 99%

“…The first publications used vaccinia virus-based constructs or peptide pools as stimulating factors (2,19,20,27). Not until recently was fine mapping of these responses achieved by using individual peptides based on different subtypes (22,28).…”

mentioning

confidence: 99%

Magnitude, Breadth, and Functional Profile of T-Cell Responses during Human Immunodeficiency Virus Primary Infection with B and BF Viral Variants

Turk

Gherardi

Laufer

et al. 2008

J Virol

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“…While CD8 ϩ T-cell cross-clade recognition has been tested extensively (6,11,19,36,48), few studies have addressed the possibility of clade-specific escape from CD8 ϩ T-cell responses. This may be especially relevant where clade consensus sequences differ in immunologically relevant epitopes.…”

Section: Hiv-specific Cd8mentioning

confidence: 99%

Clade-Specific Evolution Mediated by HLA-B*57/5801 in Human Immunodeficiency Virus Type 1 Clade A1 p24

McKinnon

Capiña

Peters

et al. 2009

J Virol

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HLA-B*57-mediated selection pressure leads to a typical escape pathway in human immunodeficiency virus type 1 (HIV-1) CD8 epitopes such as TW10. Whether this T242N pathway is shared by all clades remains unknown. We therefore assessed the nature of HLA-B*57 selection in a large, observational Kenyan cohort where clades A1 and D predominate. While T242N was ubiquitous in clade D HLA-B*57 ؉ subjects, this mutation was rare (15%) in clade A1. Instead, P243T and I247L were selected by clade A1-infected HLA-B*57 subjects but not by HLA-B*5801 ؉ subjects. Our data suggest that clade A1 consensus proline at Gag residue 243 might represent an inherent block to T242N escape in clade A1. We confirmed immunologically that P243T and I247L likely represent escape mutations. HLA-B*57 evolution also differed between clades in the KF11 and IW9 epitopes. A better understanding of clade-specific evolution is important for the development of HIV vaccines in regions with multiple clades.

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“…In addition to escape from effective immune responses, tremendous regional and global genetic diversity (Ͼ30% amino acid divergence between subtypes) poses a significant problem for HIV vaccine design: that vaccine-elicited immune responses may be unable to provide coverage for the diversity of strains a vaccinee may encounter in nature (2). Although some evidence for cross-reactivity in cellular immune responses exists (3)(4)(5)(6), how this will translate into cross-reactive protection from infection or disease progression remains controversial. Containment of challenge virus in a nonhuman primate was lost due to a single amino acid mutation in a dominant CD8 ϩ T cell epitope (7).…”

mentioning

confidence: 99%

Epitope Cross-Reactivity Frequently Differs between Central and Effector Memory HIV-Specific CD8+ T Cells

McKinnon

Ball

Wachihi

et al. 2007

The Journal of Immunology

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HIV diversity may limit the breadth of vaccine coverage due to epitope sequence differences between strains. Although amino acid substitutions within CD8+ T cell HIV epitopes can result in complete or partial abrogation of responses, this has primarily been demonstrated in effector CD8+ T cells. In an HIV-infected Kenyan cohort, we demonstrate that the cross-reactivity of HIV epitope variants differs dramatically between overnight IFN-γ and longer-term proliferation assays. For most epitopes, particular variants (not the index peptide) were preferred in proliferation in the absence of corresponding overnight IFN-γ responses and in the absence of the variant in the HIV quasispecies. Most proliferating CD8+ T cells were polyfunctional via cytokine analyses. A trend to positive correlation was observed between proliferation (but not IFN-γ) and CD4 counts. We present findings relevant to the assessment of HIV vaccine candidates and toward a better understanding of how viral diversity is tolerated by central and effector memory CD8+ T cells.

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Broad Cross-Clade T-Cell Responses to Gag in Individuals Infected with Human Immunodeficiency Virus Type 1 Non-B Clades (A to G): Importance of HLA Anchor Residue Conservation

Cited by 40 publications

References 59 publications

Magnitude, Breadth, and Functional Profile of T-Cell Responses during Human Immunodeficiency Virus Primary Infection with B and BF Viral Variants

Magnitude, Breadth, and Functional Profile of T-Cell Responses during Human Immunodeficiency Virus Primary Infection with B and BF Viral Variants

Clade-Specific Evolution Mediated by HLA-B*57/5801 in Human Immunodeficiency Virus Type 1 Clade A1 p24

Epitope Cross-Reactivity Frequently Differs between Central and Effector Memory HIV-Specific CD8+ T Cells

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