CD8+ T Cell Cross-Reactivity Profiles and HIV-1 Immune Escape towards an HLA-B35-Restricted Immunodominant Nef Epitope

Chihiro Motozono, John J. Miles, Zafrul Hasan, Hiroyuki Gatanaga, Stanley C. Meribe, David A. Price, Shinichi Oka, Andrew K. Sewell, Takamasa Ueno

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Antigen cross-reactivity is an inbuilt feature of the T cell compartment. However, little is known about the flexibility of T cell recognition in the context of genetically variable pathogens such as HIV-1. In this study, we used a combinatorial library containing 24 billion octamer peptides to characterize the cross-reactivity profiles of CD8+ T cells specific for the immunodominant HIV-1 subtype B Nef epitope VY8 (VPLRPMTY) presented by HLA-B*35:01. In conjunction, we examined naturally occurring antigenic variations within the VY8 epitope. Sequence analysis of plasma viral RNA isolated from 336 HIV-1-infected individuals revealed variability at position (P) 3 and P8 of VY8; Phe at P8, but not Val at P3, was identified as an HLA-B*35:01-associated polymorphism. VY8-specific T cells generated from several different HIV-1-infected patients showed unique and clonotype-dependent cross-reactivity footprints. Nonetheless, all T cells recognized both the index Leu and mutant Val at P3 equally well. In contrast, competitive titration assays revealed that the Tyr to Phe substitution at P8 reduced T cell recognition by 50-130 fold despite intact peptide binding to HLA-B*35:01. These findings explain the preferential selection of Phe at the C-terminus of VY8 in HLA-B*35:01+ individuals and demonstrate that HIV-1 can exploit the limitations of T cell recognition in vivo.

Original languageEnglish
Article numbere66152
JournalPloS one
Volume8
Issue number6
DOIs
Publication statusPublished - Jun 17 2013

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HLA-B35 Antigen
Immunodominant Epitopes
T-cells
Human immunodeficiency virus 1
cross reaction
HIV-1
Epitopes
T-lymphocytes
HLA-B Antigens
T-Lymphocytes
epitopes
peptides
Antigenic Variation
antigenic variation
Peptides
Viral RNA
Pathogens
titration
immunodominant epitopes
Polymorphism

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Motozono, C., Miles, J. J., Hasan, Z., Gatanaga, H., Meribe, S. C., Price, D. A., ... Ueno, T. (2013). CD8+ T Cell Cross-Reactivity Profiles and HIV-1 Immune Escape towards an HLA-B35-Restricted Immunodominant Nef Epitope. PloS one, 8(6), [e66152]. https://doi.org/10.1371/journal.pone.0066152

CD8+ T Cell Cross-Reactivity Profiles and HIV-1 Immune Escape towards an HLA-B35-Restricted Immunodominant Nef Epitope. / Motozono, Chihiro; Miles, John J.; Hasan, Zafrul; Gatanaga, Hiroyuki; Meribe, Stanley C.; Price, David A.; Oka, Shinichi; Sewell, Andrew K.; Ueno, Takamasa.

In: PloS one, Vol. 8, No. 6, e66152, 17.06.2013.

Research output: Contribution to journalArticle

Motozono, C, Miles, JJ, Hasan, Z, Gatanaga, H, Meribe, SC, Price, DA, Oka, S, Sewell, AK & Ueno, T 2013, 'CD8+ T Cell Cross-Reactivity Profiles and HIV-1 Immune Escape towards an HLA-B35-Restricted Immunodominant Nef Epitope', PloS one, vol. 8, no. 6, e66152. https://doi.org/10.1371/journal.pone.0066152
Motozono, Chihiro ; Miles, John J. ; Hasan, Zafrul ; Gatanaga, Hiroyuki ; Meribe, Stanley C. ; Price, David A. ; Oka, Shinichi ; Sewell, Andrew K. ; Ueno, Takamasa. / CD8+ T Cell Cross-Reactivity Profiles and HIV-1 Immune Escape towards an HLA-B35-Restricted Immunodominant Nef Epitope. In: PloS one. 2013 ; Vol. 8, No. 6.
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