Mutational Escape in HIV-1 CTL Epitopes Leads to Increased Binding to Inhibitory Myelomonocytic MHC Class I Receptors
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 C...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science,
2011-07-20T21:05:06Z.
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| Subjects: | |
| Online Access: | Get fulltext |
| Summary: | 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. National Institutes of Health (U.S.) (Grant R01 AI078799) National Institutes of Health (U.S.) (Grant P01 AI074415) Doris Duke Charitable Foundation |
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