Mutational escape in HIV-1 CTL epitopes leads to increased binding to inhibitory myelomonocytic MHC class I receptors.

• Main Authors: Yue Yang, Jinghe Huang, Ildiko Toth, Mathias Lichterfeld, Xu G Yu
• Format: Article
• Language: English
• Published: Public Library of Science (PLoS) 2010-12-01
• Series: PLoS ONE
• Online Access: http://europepmc.org/articles/PMC2999561?pdf=render

Escape mutations in HIV-1 cytotoxic T cell (CTL) epitopes can abrogate recognition by the TCR of HIV-1-specific CD8+ T cells, but may also change interactions with alternative MHC class I receptors. Here, we show that mutational escape in three HLA-A11-, B8- and B7- restricted immunodominant HIV-1 CTL epitopes consistently enhances binding of the respective peptide/MHC class I complex to Immunoglobulin-like transcript 4 (ILT4), an inhibitory myelomonocytic MHC class I receptor expressed on monocytes and dendritic cells. In contrast, mutational escape in an alternative immunodominant HLA-B57-restricted CTL epitope did not affect ILT4-mediated recognition by myelomonocytic cells. This suggests that in addition to abrogating recognition by HIV-1-specific CD8 T cells, mutational escape in some, but not all CTL epitopes may mediate important immunoregulatory effects by increasing binding properties to ILT4, and augmenting ILT4-mediated inhibitory effects of professional antigen-presenting cells.