Distinct differentiation profiles of HIV-Gag and Nef-specific central memory CD8+ T cells associated with HLA-B57/5801 and virus control

Xie, Jun; Lü, Wei; Samri, Assia; Costagliola, Dominique; Schnuriger, Aurélie; Silva, Bosco Christiano Maciel da; Blanc, Catherine; Larsen, Martin; Théodorou, Ioannis; Rouzioux, Christine; Autran, Brigitte

doi:10.1097/qad.0b013e32833e5009

Cited by 19 publications

(22 citation statements)

References 31 publications

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“…on May 9, 2018. by guest www.bloodjournal.org From ALT cohort: 2.29 log copies/10 6 PBMCs; IQR, 1.53-2.89 log copies/ 10 6 PBMCs; n ϭ 50). 36 Thus, our results on a large group of HICs extend previous observations and confirm that HICs have a remarkably small HIV reservoir.…”

Section: Hic Cd4 ؉ T-cell Permissiveness To Hiv-1 Replication Correlasupporting

confidence: 80%

Restriction of HIV-1 replication in macrophages and CD4+ T cells from HIV controllers

Sáez‐Cirión

Hamimi

Bergamaschi

et al. 2011

Blood

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104

103

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Section: Hic Cd4 ؉ T-cell Permissiveness To Hiv-1 Replication Correlasupporting

confidence: 80%

Restriction of HIV-1 replication in macrophages and CD4+ T cells from HIV controllers

Sáez‐Cirión

Hamimi

Bergamaschi

et al. 2011

Blood

Self Cite

104

103

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“…Additional evidence implicates altered major histocompatibility complex (MHC) class I peptide binding resulting in superior viral recognition; specific amino acid residues within the MHC class I peptide-binding groove were associated with control (5), and an in silico model of thymic selection with the HLA-B*5701 allele resulted in a higher proportion of naive T cells able to recognize viral epitopes and cross-react with mutants of targeted epitopes (6). Other studies have also shown evidence for a CD8 ϩ T cell-based mechanism of control at the cellular level (7,8). Together, this evidence suggests differential peptide presentation as a possible mechanism of viral control associated with HLA-B alleles: presentation of viral peptides that promote superior CD8 ϩ T cell activation or that are crucial to viral fitness may ultimately result in reduced viral immune evasion and effective suppression.…”

Section: Importancementioning

confidence: 99%

Divergent Antibody Subclass and Specificity Profiles but Not Protective HLA-B Alleles Are Associated with Variable Antibody Effector Function among HIV-1 Controllers

Lai

Licht

Dugast

et al. 2014

J Virol

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Understanding the coordination between humoral and cellular immune responses may be the key to developing protective vaccines, and because genetic studies of long-term HIV-1 nonprogressors have associated specific HLA-B alleles with spontaneous control of viral replication, this subject group presents an opportunity to investigate relationships between arms of the adaptive immune system. Given evidence suggesting that cellular immunity may play a role in viral suppression, we sought to determine whether and how the humoral immune response might vary among controllers. Significantly, Fc-mediated antibody effector functions have likewise been associated with durable viral control. In this study, we compared the effector function and biophysical features of HIV-specific antibodies in a cohort of controllers with and without protective HLA-B alleles in order to investigate whether there was evidence for multiple paths to HIV-1 control, or whether cellular and humoral arms of immunity might exhibit coordinated profiles. However, with the exception of IgG2 antibodies to gp41, HLA status was not associated with divergent humoral responses. This finding did not result from uniform antibody responses across subjects, as controllers could be regrouped according to strong differences in their HIV-specific antibody subclass specificity profiles. These divergent antibody profiles were further associated with significant differences in nonneutralizing antibody effector function, with levels of HIVspecific IgG1 acting as the major distinguishing factor. Thus, while HLA background among controllers was associated with minimal differences in humoral function, antibody subclass and specificity profiles were associated with divergent effector function, suggesting that these features could be used to make functional predictions. Because these nonneutralizing antibody activities have been associated with spontaneous viral control, reduced viral load, and nonprogression in infected subjects and protection in vaccinated subjects, understanding the specific features of IgGs with potentiated effector function may be critical to vaccine and therapeutic antibody development. IMPORTANCEIn this study, we investigated whether the humoral and cellular arms of adaptive immunity exhibit coordinated or compensatory activity by studying the antibody response among HIV-1 controllers with different genetic backgrounds.

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“…Strong CD8 responses to HIV-gag are often reported in elite controllers with subsequent production of cytotoxic granules, IL-2 and IFN-g, and cell surface expression of CD27 leading to high functional avidity [35,[37][38][39]. CD8 cells also demonstrate antiviral effects by inhibiting virus production from super-infected CD4 cells in elite controllers [36,38].…”

Section: Controllers and Ltnpmentioning

confidence: 99%

“…There is evidence suggesting that an adaptive MHC class I-restricted CD8-mediated control is operating, given the linkage between the MHC class I locus and elite controllers [9,[35][36][37]. Strong CD8 responses to HIV-gag are often reported in elite controllers with subsequent production of cytotoxic granules, IL-2 and IFN-g, and cell surface expression of CD27 leading to high functional avidity [35,[37][38][39].…”

Section: Controllers and Ltnpmentioning

confidence: 99%

Elite Controllers and Long-term Nonprogressors: Models for HIV Vaccine Development?

Okulicz¹

2012

J AIDS Clinic Res

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Distinct differentiation profiles of HIV-Gag and Nef-specific central memory CD8+ T cells associated with HLA-B57/5801 and virus control

Abstract: HLA-B57/5801 drives a preferential CD27(+) differentiation of central memory CD8(+) T cells directed against HIV-Gag but not Nef that may contribute to the ability of Gag-specific CD8(+) T cells to better control HIV in HLA-B57/5801 nonprogressors.

Cited by 19 publications

References 31 publications

Restriction of HIV-1 replication in macrophages and CD4+ T cells from HIV controllers

Restriction of HIV-1 replication in macrophages and CD4+ T cells from HIV controllers

Divergent Antibody Subclass and Specificity Profiles but Not Protective HLA-B Alleles Are Associated with Variable Antibody Effector Function among HIV-1 Controllers

Elite Controllers and Long-term Nonprogressors: Models for HIV Vaccine Development?

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