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 ORCID: https://orcid.org/0000-0001-9416-2737, Oka, Shinichi, Sewell, Andrew K. ORCID: https://orcid.org/0000-0003-3194-3135 and Ueno, Takamasa 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. 10.1371/journal.pone.0066152

Preview

PDF - Published Version Available under License Creative Commons Attribution. Download (423kB) | Preview

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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Subjects:	Q Science > QR Microbiology > QR180 Immunology
Publisher:	Public Library of Science
ISSN:	1932-6203
Date of First Compliant Deposit:	1 April 2016
Last Modified:	10 Jun 2023 16:55
URI:	https://orca.cardiff.ac.uk/id/eprint/88527

Citation Data

Cited 5 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item