Conformational instability governed by disulfide bonds partitions the dominant from subdominant helper T-cell responses specific for HIV-1 envelope glycoprotein gp120

Background: : The diversity of the HIV proteome influences the cellular response and development of an effective vaccine, particularly due to the generation of viral variants with mutations located within CD8+ T-cell epitopes. These mutations can affect the recognition of the epitopes, that may result in the selection of HIV variants with mutated epitopes (autologous epitopes) and different CD8+ T-cell functional profiles. Objective:: To determine the phenotype and functionality of CD8+ T-cell from HIV-infected Colombian patients in response to autologous and consensus peptides derived from HIV-1 clade B protease and reverse transcriptase (RT). Methods:: By flow cytometry, we compared the ex vivo CD8+ T-cell responses from HIV-infected patients to autologous and consensus peptides derived from HIV-1 clade B protease and RT, restricted by HLA-B*35, HLA-B*44 and HLA-B*51 alleles. Results:: Although autologous peptides restricted by HLA-B*35 and HLA-B*44 did not show any differences compared with consensus peptides, we observed the induction of a higher polyfunctional profile of CD8+ T-cells by autologous peptides restricted by HLA-B*51, particularly by the production of interferon-γ and macrophage inflammatory protein-1β. The response by different memory CD8+ T-cell populations was comparable between autologous vs. consensus peptides. In addition, the magnitude of the polyfunctional response induced by the HLA-B*51-restricted QRPLVTIRI autologous epitope correlated with low viremia. Conclusion:: Autologous peptides should be considered for the evaluation of HIV-specific CD8+ Tcell responses and to reveal some relevant epitopes that could be useful for therapeutic strategies aiming to promote polyfunctional CD8+ T-cell responses in a specific population of HIV-infected patients.

Download Full-text

Expression of placenta-specific 1 and its potential for eliciting anti-tumor helper T-cell responses in head and neck squamous cell carcinoma

OncoImmunology ◽

10.1080/2162402x.2020.1856545 ◽

2020 ◽

Vol 10 (1) ◽

pp. 1856545

Author(s):

Ryusuke Hayashi ◽

Toshihiro Nagato ◽

Takumi Kumai ◽

Kenzo Ohara ◽

Mizuho Ohara ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

T Cell ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

T Cell Responses ◽

Neck Squamous Cell Carcinoma ◽

Helper T Cell ◽

Cell Responses

Download Full-text

Exploiting knowledge of immune selection in HIV-1 to detect HIV-specific CD8 T-cell responses

Vaccine ◽

10.1016/j.vaccine.2010.06.091 ◽

2010 ◽

Vol 28 (37) ◽

pp. 6052-6057 ◽

Cited By ~ 8

Author(s):

Coral-Ann M. Almeida ◽

Steven G. Roberts ◽

Rebecca Laird ◽

Elizabeth McKinnon ◽

Imran Ahmad ◽

...

Keyword(s):

T Cell ◽

T Cell Responses ◽

Cd8 T Cell ◽

Immune Selection ◽

Cell Responses ◽

Hiv 1

Download Full-text

Higher T-Cell Responses Induced by DNA/rAd5 HIV-1 Preventive Vaccine Are Associated With Lower HIV-1 Infection Risk in an Efficacy Trial

The Journal of Infectious Diseases ◽

10.1093/infdis/jix086 ◽

2017 ◽

Vol 215 (9) ◽

pp. 1376-1385 ◽

Cited By ~ 32

Author(s):

Holly E. Janes ◽

Kristen W. Cohen ◽

Nicole Frahm ◽

Stephen C. De Rosa ◽

Brittany Sanchez ◽

...

Keyword(s):

T Cell ◽

T Cell Responses ◽

Infection Risk ◽

Efficacy Trial ◽

Cell Responses ◽

Preventive Vaccine ◽

Hiv 1

Download Full-text

Combination of Immune and Viral Factors Distinguishes Low-Risk versus High-Risk HIV-1 Disease Progression in HLA-B*5701 Subjects

Journal of Virology ◽

10.1128/jvi.01165-12 ◽

2012 ◽

Vol 86 (18) ◽

pp. 9802-9816 ◽

Cited By ~ 17

Author(s):

Melissa M. Norström ◽

Marcus Buggert ◽

Johanna Tauriainen ◽

Wendy Hartogensis ◽

Mattia C. Prosperi ◽

...

Keyword(s):

T Cell ◽

High Risk ◽

High Resolution ◽

Disease Progression ◽

T Cell Responses ◽

Low Risk ◽

Early Infection ◽

Cell Responses ◽

Cell Counts ◽

Hiv 1

HLA-B*5701 is the host factor most strongly associated with slow HIV-1 disease progression, although rates can vary within this group. Underlying mechanisms are not fully understood but likely involve both immunological and virological dynamics. The present study investigated HIV-1in vivoevolution and epitope-specific CD8+T cell responses in six HLA-B*5701 patients who had not received antiretroviral treatment, monitored from early infection for up to 7 years. The subjects were classified as high-risk progressors (HRPs) or low-risk progressors (LRPs) based on baseline CD4+T cell counts. Dynamics of HIV-1 Gag p24 evolution and multifunctional CD8+T cell responses were evaluated by high-resolution phylogenetic analysis and polychromatic flow cytometry, respectively. In all subjects, substitutions occurred more frequently in flanking regions than in HLA-B*5701-restricted epitopes. In LRPs, p24 sequence diversity was significantly lower; sequences exhibited a higher degree of homoplasy and more constrained mutational patterns than HRPs. The HIV-1 intrahost evolutionary rate was also lower in LRPs and followed a strict molecular clock, suggesting neutral genetic drift rather than positive selection. Additionally, polyfunctional CD8+T cell responses, particularly to TW10 and QW9 epitopes, were more robust in LRPs, who also showed significantly higher interleukin-2 (IL-2) production in early infection. Overall, the findings indicate that HLA-B*5701 patients with higher CD4 counts at baseline have a lower risk of HIV-1 disease progression because of the interplay between specific HLA-linked immune responses and the rate and mode of viral evolution. The study highlights the power of a multidisciplinary approach, integrating high-resolution evolutionary and immunological data, to understand mechanisms underlying HIV-1 pathogenesis.

Download Full-text

Comprehensive Epitope Analysis of Human Immunodeficiency Virus Type 1 (HIV-1)-Specific T-Cell Responses Directed against the Entire Expressed HIV-1 Genome Demonstrate Broadly Directed Responses, but No Correlation to Viral Load

Journal of Virology ◽

10.1128/jvi.77.3.2081-2092.2003 ◽

2003 ◽

Vol 77 (3) ◽

pp. 2081-2092 ◽

Cited By ~ 513

Author(s):

M. M. Addo ◽

X. G. Yu ◽

A. Rathod ◽

D. Cohen ◽

R. L. Eldridge ◽

...

Keyword(s):

T Cell ◽

T Cell Responses ◽

Protein Subunits ◽

Cell Responses ◽

Cellular Immune Responses ◽

Immunodeficiency Virus ◽

Total Magnitude ◽

Cellular Immune ◽

Hiv 1

ABSTRACT Cellular immune responses play a critical role in the control of human immunodeficiency virus type 1 (HIV-1); however, the breadth of these responses at the single-epitope level has not been comprehensively assessed. We therefore screened peripheral blood mononuclear cells (PBMC) from 57 individuals at different stages of HIV-1 infection for virus-specific T-cell responses using a matrix of 504 overlapping peptides spanning all expressed HIV-1 proteins in a gamma interferon-enzyme-linked immunospot (Elispot) assay. HIV-1-specific T-cell responses were detectable in all study subjects, with a median of 14 individual epitopic regions targeted per person (range, 2 to 42), and all 14 HIV-1 protein subunits were recognized. HIV-1 p24-Gag and Nef contained the highest epitope density and were also the most frequently recognized HIV-1 proteins. The total magnitude of the HIV-1-specific response ranged from 280 to 25,860 spot-forming cells (SFC)/106 PBMC (median, 4,245) among all study participants. However, the number of epitopic regions targeted, the protein subunits recognized, and the total magnitude of HIV-1-specific responses varied significantly among the tested individuals, with the strongest and broadest responses detectable in individuals with untreated chronic HIV-1 infection. Neither the breadth nor the magnitude of the total HIV-1-specific CD8+-T-cell responses correlated with plasma viral load. We conclude that a peptide matrix-based Elispot assay allows for rapid, sensitive, specific, and efficient assessment of cellular immune responses directed against the entire expressed HIV-1 genome. These data also suggest that the impact of T-cell responses on control of viral replication cannot be explained by the mere quantification of the magnitude and breadth of the CD8+-T-cell response, even if a comprehensive pan-genome screening approach is applied.

Download Full-text