Enhanced Detection of Human Immunodeficiency Virus Type 1 (HIV-1) Nef-Specific T Cells Recognizing Multiple Variants in Early HIV-1 Infection

Malhotra, Uma; Li, Fusheng; Nolin, Jessica; Allison, Megan; Zhao, Hong; Mullins, James I.; Self, Steve; McElrath, M. Juliana

doi:10.1128/jvi.02564-06

Cited by 44 publications

(65 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Single-peptide-based screening of T-cell responses allowed fine mapping, which revealed broad crossclade T-cell populations, although clade-specific magnitude, breadth, and domain targeting were observed. Immunodominance of the Nef central region was demonstrated in our cohort, in accordance with other studies (22,26,28,35,43,45). Most of the cross-reactive peptides clustered in this conserved region of the protein.…”

Section: Discussionsupporting

confidence: 79%

“…2A and B). This observation has also been reported previously for subtype B and other subtypes (22,26,28,35,43,45). However, in this study, clade-specific differences in targeted Nef domains were observed.…”

Section: Study Subjectscontrasting

confidence: 54%

“…The third explanation was found as the main putative cause accounting for the lack of recognition of one of the peptides within a discordant pair. On the other hand, recent studies have shown that while different variants of a given epitope may be recognized by T cells, variation in the epitope sequence has a profound impact on the ability of CTLs to recognize and clear infected cells (9,45). Here, we demonstrated that there exist significant differences in the quality (cytokine secretion profile and cytotoxic activity) and magnitude of the CD8 response to different epitope variants.…”

Section: Discussionmentioning

confidence: 63%

“…Results were expressed as spotforming units (SFU)/10 6 PBMCs after subtraction of the negative-control values. Thresholds for positive responses for the test wells were defined as at least 50 SFU/10 6 PBMCs or as mean SFU greater than three times the mean SFU of the negative-control wells, whichever was higher (19,36,45,46). Confirmation of individual peptide responses was performed in triplicate.…”

mentioning

confidence: 99%

See 3 more Smart Citations

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

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionsupporting

confidence: 79%

Section: Study Subjectscontrasting

confidence: 54%

Section: Discussionmentioning

confidence: 63%

mentioning

confidence: 99%

See 2 more Smart Citations

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

View full text Add to dashboard Cite

show abstract

“…The PTE approach is based on a biometric algorithm that includes frequently found kmer sequences from circulating strains in a sequence database to build a standardized panel of HIV peptides for CTL based vaccine evaluation (35). Similarly to the toggled peptides, PTE peptides detect significantly more and stronger responses than consensus based peptides (36). Toggled peptides and PTE peptides each have different virtues and issues.…”

Section: Discussionmentioning

confidence: 99%

Increased Sequence Diversity Coverage Improves Detection of HIV-Specific T Cell Responses

Frahm

Kaufmann

Yusim

et al. 2007

The Journal of Immunology

View full text Add to dashboard Cite

The accurate identification of HIV-specific T cell responses is important for determining the relationship between immune response, viral control, and disease progression. HIV-specific immune responses are usually measured using peptide sets based on consensus sequences, which frequently miss responses to regions where test set and infecting virus differ. In this study, we report the design of a peptide test set with significantly increased coverage of HIV sequence diversity by including alternative amino acids at variable positions during the peptide synthesis step. In an IFN-γ ELISpot assay, these “toggled” peptides detected HIV-specific CD4+ and CD8+ T cell responses of significantly higher breadth and magnitude than matched consensus peptides. The observed increases were explained by a closer match of the toggled peptides to the autologous viral sequence. Toggled peptides therefore afford a cost-effective and significantly more complete view of the host immune response to HIV and are directly applicable to other variable pathogens.

show abstract

Characterization of Gag and Nef-specific ELISpot-based CTL responses in HIV-1 infected Indian individuals

Mendiratta

Vajpayee

Malhotra

et al. 2008

Med Microbiol Immunol

Self Cite

View full text Add to dashboard Cite

Cytotoxic T lymphocyte (CTL) responses to Gag have been most frequently linked to control of viremia whereas CTL responses to Nef have direct relationship with viral load. IFN-gamma ELISpot assay was used to screen CTL responses at single peptide level directed at HIV-1 subtype C Gag and Nef proteins in 30 antiretroviral therapy naive HIV-1 infected Indian individuals. PBMCs from 73.3% and 90% of the study population showed response to Gag and Nef antigens, respectively. The magnitude of Gag-specific CTL responses was inversely correlated with plasma viral load (r = -0.45, P = 0.001), whereas magnitude of Nef-specific responses was directly correlated (r = 0.115). Thirteen immunodominant regions (6 in Gag, 7 in Nef) were identified in the current study. The identification of Gag and Nef-specific responses across HIV-1 infected Indian population and targeting epitopes from multiple immunodominant regions may provide useful insight into the designing of new immunotherapy and vaccines.

show abstract

Enhanced Detection of Human Immunodeficiency Virus Type 1 (HIV-1) Nef-Specific T Cells Recognizing Multiple Variants in Early HIV-1 Infection

Cited by 44 publications

References 45 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

Increased Sequence Diversity Coverage Improves Detection of HIV-Specific T Cell Responses

Characterization of Gag and Nef-specific ELISpot-based CTL responses in HIV-1 infected Indian individuals

Contact Info

Product

Resources

About