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A viral CTL escape mutation leading to immunoglobulin-like transcript 4-mediated functional inhibition of myelomonocytic cells.
- Source :
-
The Journal of experimental medicine [J Exp Med] 2007 Nov 26; Vol. 204 (12), pp. 2813-24. Date of Electronic Publication: 2007 Nov 19. - Publication Year :
- 2007
-
Abstract
- Viral mutational escape can reduce or abrogate recognition by the T cell receptor (TCR) of virus-specific CD8+ T cells. However, very little is known about the impact of cytotoxic T lymphocyte (CTL) epitope mutations on interactions between peptide-major histocompatibility complex (MHC) class I complexes and MHC class I receptors expressed on other cell types. Here, we analyzed a variant of the immunodominant human leukocyte antigen (HLA)-B2705-restricted HIV-1 Gag KK10 epitope (KRWIILGLNK) with an L to M amino acid substitution at position 6 (L6M), which arises as a CTL escape variant after primary infection but is sufficiently immunogenic to elicit a secondary, de novo HIV-1-specific CD8+ T cell response with an alternative TCR repertoire in chronic infection. In addition to altering recognition by HIV-1-specific CD8+ T cells, the HLA-B2705-KK10 L6M complex also exhibits substantially increased binding to the immunoglobulin-like transcript (ILT) receptor 4, an inhibitory MHC class I-specific receptor expressed on myelomonocytic cells. Binding of the B2705-KK10 L6M complex to ILT4 leads to a tolerogenic phenotype of myelomonocytic cells with lower surface expression of dendritic cell (DC) maturation markers and co-stimulatory molecules. These data suggest a link between CTL-driven mutational escape, altered recognition by innate MHC class I receptors on myelomonocytic cells, and functional impairment of DCs, and thus provide important new insight into biological consequences of viral sequence diversification.
- Subjects :
- Acquired Immunodeficiency Syndrome genetics
HIV genetics
HLA-B27 Antigen genetics
Histocompatibility Antigens Class I genetics
Humans
Monocytes virology
Mutation
Myeloid Cells virology
Receptors, Antigen, T-Cell genetics
Acquired Immunodeficiency Syndrome immunology
CD8-Positive T-Lymphocytes immunology
CD8-Positive T-Lymphocytes virology
HIV immunology
HIV Infections immunology
Monocytes immunology
Myeloid Cells immunology
T-Lymphocytes, Cytotoxic immunology
T-Lymphocytes, Cytotoxic virology
Subjects
Details
- Language :
- English
- ISSN :
- 1540-9538
- Volume :
- 204
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- The Journal of experimental medicine
- Publication Type :
- Academic Journal
- Accession number :
- 18025130
- Full Text :
- https://doi.org/10.1084/jem.20061865