Characteristics of HIV-1 Nef Regions Containing Multiple CD8+ T Cell Epitopes: Wealth of HLA-Binding Motifs and Sensitivity to Proteasome Degradation - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Journal of Immunology Année : 2001

Characteristics of HIV-1 Nef Regions Containing Multiple CD8+ T Cell Epitopes: Wealth of HLA-Binding Motifs and Sensitivity to Proteasome Degradation

Jeannine Choppin
  • Fonction : Auteur
William Cohen
  • Fonction : Auteur
Alberto Bianco
  • Fonction : Auteur
  • PersonId : 931330
Jean-Paul Briand
  • Fonction : Auteur
  • PersonId : 931467
Francine Connan
  • Fonction : Auteur
Marc Dalod
Jean-Gérard Guillet
  • Fonction : Auteur

Résumé

First and foremost among the many factors that influence epitope presentation are the degradation of Ag, which results in peptide liberation, and the presence of HLA class I molecules able to present the peptides to T lymphocytes. To define the regions of HIV-1 Nef that can provide multiple T cell epitopes, we analyzed the Nef sequence and determined that there are 73 peptides containing 81 HLA-binding motifs. We tested the binding of these peptides to six common HLA molecules (HLA-A2, -A3, -A24, -B7, -B8, and -B35), and we showed that most of them were efficient binders (54% of motifs), especially peptides associating with HLA-A3, -B7/35, and -B8 molecules. Nef peptides most frequently recognized by T cells of HIV-1-infected individuals were 90–97, 135–143, 71–81, 77–85, 90–100, 73–82, and 128–137. The frequency of T cell recognition was not directly related to the strength of peptide-HLA binding. The generation of Nef epitopes is crucial; therefore, we investigated the digestion by the 20S proteasome of a large peptide, Nef66–100. This fragment was efficiently cleaved, and NH2-terminally extended precursors of epitope 71–81 were recognized by T cells of an HIV-1-infected individual. These results suggest that a high frequency of T cell recognition may depend on proteasome cleavage.

Domaines

Immunologie

Dates et versions

hal-03338644 , version 1 (08-09-2021)

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Citer

Jeannine Choppin, William Cohen, Alberto Bianco, Jean-Paul Briand, Francine Connan, et al.. Characteristics of HIV-1 Nef Regions Containing Multiple CD8+ T Cell Epitopes: Wealth of HLA-Binding Motifs and Sensitivity to Proteasome Degradation. Journal of Immunology, 2001, 166 (10), pp.6164-6169. ⟨10.4049/jimmunol.166.10.6164⟩. ⟨hal-03338644⟩

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