Epitope length variants balance protective immune responses and viral escape in HIV-1 infection
Research output: Contribution to journal › Journal article › Research › peer-review
Documents
- Fulltext
Final published version, 5.14 MB, PDF document
Cytotoxic T lymphocyte (CTL) and natural killer (NK) cell responses to a single optimal 10-mer epitope (KK10) in the human immunodeficiency virus type-1 (HIV-1) protein p24Gag are associated with enhanced immune control in patients expressing human leukocyte antigen (HLA)-B∗27:05. We find that proteasomal activity generates multiple length variants of KK10 (4–14 amino acids), which bind TAP and HLA-B∗27:05. However, only epitope forms ≥8 amino acids evoke peptide length-specific and cross-reactive CTL responses. Structural analyses reveal that all epitope forms bind HLA-B∗27:05 via a conserved N-terminal motif, and competition experiments show that the truncated epitope forms outcompete immunogenic epitope forms for binding to HLA-B∗27:05. Common viral escape mutations abolish (L136M) or impair (R132K) production of KK10 and longer epitope forms. Peptide length influences how well the inhibitory NK cell receptor KIR3DL1 binds HLA-B∗27:05 peptide complexes and how intraepitope mutations affect this interaction. These results identify a viral escape mechanism from CTL and NK responses based on differential antigen processing and peptide competition.
Original language | English |
---|---|
Article number | 110449 |
Journal | Cell Reports |
Volume | 38 |
Issue number | 9 |
Number of pages | 22 |
ISSN | 2211-1247 |
DOIs | |
Publication status | Published - 2022 |
Bibliographical note
Publisher Copyright:
© 2022 The Author(s)
- crystal structures, cytotoxic T lymphocytes, differential antigen processing, HIV-1, HLA-B27:05, immune-response inhibition, KIR3DL1, natural killer cells, peptide competition, viral escape
Research areas
ID: 314279016