Aminopeptidase substrate preference affects HIV epitope presentation and predicts immune escape patterns in HIV-infected individuals.

The Journal of Immunology : Official Journal of the American Association of Immunologists
Shao Chong ZhangSylvie Le Gall

Abstract

Viruses evade immune detection partly through immune-associated mutations. Analyses of HIV sequences derived from infected individuals have identified numerous examples of HLA-associated mutations within or adjacent to T cell epitopes, but the potential impact of most mutations on epitope production and presentation remains unclear. The multistep breakdown of proteins into epitopes includes trimming of N-extended peptides into epitopes by aminopeptidases before loading onto MHC class I molecules. Definition of sequence signatures that modulate epitope production would lead to a better understanding of factors driving viral evolution and immune escape at the population level. In this study, we identified cytosolic aminopeptidases cleavage preferences in primary cells and its impact on HIV Ag degradation into epitopes in primary human cell extracts by mass spectrometry and on epitope presentation to CTL. We observed a hierarchy of preferred amino acid cleavage by cytosolic aminopeptidases. We demonstrated that flanking mutations producing more or less cleavable motifs can increase or decrease epitope production and presentation by up to 14-fold. We found that the efficiency of epitope production correlates with cleavability of fl...Continue Reading

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Citations

Apr 30, 2014·Cancer Immunology Research·Nir HacohenCatherine J Wu
Jul 6, 2017·Human Vaccines & Immunotherapeutics·Xintao HuBarbara K Felber
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Sep 19, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jens DinterSylvie Le Gall
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Apr 11, 2018·Molecular Immunology·Julie Boucau, Sylvie Le Gall
Aug 7, 2013·Molecular Immunology·Carlos Alvarez-Navarro, José A López de Castro

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