The presence of prolines in the flanking region of an immunodominant HIV‐2 gag epitope influences the quality and quantity of the epitope generated

Abstract

Both the recognition of HIV‐infected cells and the immunogenicity of candidate CTL vaccines depend on the presentation of a peptide epitope at the cell surface, which in turn depends on intracellular antigen processing. Differential antigen processing maybe responsible for the differences in both the quality and the quantity of epitopes produced, influencing the immunodominance hierarchy of viral epitopes. Previously, we showed that the magnitude of the HIV‐2 gag‐specific T‐cell response is inversely correlated with plasma viral load, particularly when responses are directed against an epitope, 165DRFYKSLRA173, within the highly conserved Major Homology Region of gag‐p26. We also showed that the presence of three proline residues, at positions 119, 159 and 178 of gag‐p26, was significantly correlated with low viral load. Since this proline motif was also associated with stronger gag‐specific CTL responses, we investigated the impact of these prolines on proteasomal processing of the protective 165DRFYKSLRA173 epitope. Our data demonstrate that the 165DRFYKSLRA173 epitope is most efficiently processed from precursors that contain two flanking proline residues, found naturally in low viral‐load patients. Superior antigen processing and enhanced presentation may account for the link between infection with HIV‐2 encoding the “PPP‐gag” sequence and both strong gag‐specific CTL responses as well as lower viral load.

Conformational maps of human 20S proteasomes reveal PA28- and immuno-dependent inter-ring crosstalks

“…binding to PA28αβ or PA28γ. For this, we purchased commercial i20S purified from human spleen previously used for in vitro proteolytic assays [42][43][44] . We obtained 89% subunit sequence coverage on average for the 17 subunits of the std/i20S ( Supplementary Fig.…”

Immunodominance complexity: lessons yet to be learned from dominant T cell responses to SARS-COV-2

“…The sequence either side of an epitope can affect proteasomal digestion, potentially decreasing, or even increasing, epitope generation. The presence of two proline residues at position 159 and 178 of HIV-1 gag-p26 were demonstrated to enhance antigen processing and presentation efficiency [ 30 ].…”

HLA-associated polymorphisms in the HIV-2 capsid highlight key differences between HIV-1 and HIV-2 immune adaptation

“…1 ). Changes in flanking residues can affect epitope processing and presentation, therefore, influencing CTL response [ 24 ].…”