Identification of native and posttranslationally modified HLA-B*57:01- restricted HIV envelope derived epitopes using immunoproteomics

Sri H. Ramarathinam, Stephanie Gras, Sheilajen Alcantara, Amanda W.S. Yeung, Nicole A. Mifsud, Secondo Sonza, Patricia Illing, Elias N Glaros, Robert J. Center, Shane R. Thomas, Stephen J. Kent, Nicola Ternette, Damian F J Purcell, Jamie Rossjohn, Anthony W. Purcell

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12 Citations (Scopus)

Abstract

The recognition of pathogen‐derived peptides by T lymphocytes is the cornerstone of adaptive immunity, whereby intracellular antigens are degraded in the cytosol and short peptides assemble with class I human leukocyte antigen (HLA) molecules in the ER. These peptide‐HLA complexes egress to the cell surface and are scrutinized by cytotoxic CD8+ T‐cells leading to the eradication of the infected cell. Here, naturally presented HLA‐B*57:01 bound peptides derived from the envelope protein of the human immunodeficiency virus (HIVenv) are identified. HIVenv peptides are present at a very small percentage of the overall HLA‐B*57:01 peptidome (<0.1%) and both native and posttranslationally modified forms of two distinct HIV peptides are identified. Notably, a peptide bearing a natively encoded C‐terminal tryptophan residue is also present in a modified form containing a kynurenine residue. Kynurenine is a major product of tryptophan catabolism and is abundant during inflammation and infection. Binding of these peptides at a molecular level and their immunogenicity in preliminary functional studies are examined. Modest immune responses are observed to the modified HIVenv peptide, highlighting a potential role for kynurenine‐modified peptides in the immune response to HIV and other viral infections.
Original languageEnglish
Article number1700253
Number of pages11
JournalProteomics
Volume18
Issue number12
DOIs
Publication statusPublished - Jun 2018

Keywords

  • HLA-B*57:01
  • immunopeptidome
  • human immunodeficiency virus
  • kynurenine
  • posttranslational modification

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