title: Mutational escape in HIV-1 CTL epitopes leads to increased binding to inhibitory myelomonocytic MHC class I receptors.
abstract: 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.
authors.affiliation: Ragon Institute of Massachusetts General Hospital, Harvard and MIT, Boston, Massachusetts, United States of America. xyu@partners.org
authors.forename: Yue
authors.initials: Y
authors.lastname: Yang
authors.forename: Jinghe
authors.initials: J
authors.lastname: Huang
authors.forename: Ildiko
authors.initials: I
authors.lastname: Toth
authors.forename: Mathias
authors.initials: M
authors.lastname: Lichterfeld
authors.forename: Xu G
authors.initials: XG
authors.lastname: Yu
mesh_terms: D018122:B7-1 Antigen / Q000737:chemistry; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology; D004252:DNA Mutational Analysis; D000939:Epitopes / Q000737:chemistry; D005805:Genes, MHC Class I; D015497:HIV-1 / Q000378:metabolism*; D015235:HLA-B Antigens / Q000737:chemistry*; D015395:Histocompatibility Antigens Class I / Q000737:chemistry*; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000096:biosynthesis; D008562:Membrane Glycoproteins / Q000737:chemistry; D009000:Monocytes / Q000166:cytology*; D009154:Mutation; D010455:Peptides / Q000737:chemistry; D011971:Receptors, Immunologic / Q000737:chemistry; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000821:virology
chemical_list: D018122:B7-1 Antigen; D000939:Epitopes; D015235:HLA-B Antigens; C103707:HLA-B57 antigen; D015395:Histocompatibility Antigens Class I; C491341:LILRB2 protein, human; D018950:Lipopolysaccharide Receptors; D008562:Membrane Glycoproteins; D010455:Peptides; D011971:Receptors, Immunologic