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A viral CTL escape mutation leading to immunoglobulin-like transcript 4-mediated functional inhibition of myelomonocytic cells

Lichterfeld, M; Kavanagh, DG; Williams, KL; Moza, B; Mui, SK; Miura, T; Sivamurthy, R; Allgaier, R; Pereyra, F; Trocha, A; et al. Lichterfeld, M; Kavanagh, DG; Williams, KL; Moza, B; Mui, SK; Miura, T; Sivamurthy, R; Allgaier, R; Pereyra, F; Trocha, A; Feeney, M; Gandhi, RT; Rosenberg, ES; Altfeld, M; Allen, TM; Allen, R; Walker, BD; Sundberg, EJ; Yu, XG (2007) A viral CTL escape mutation leading to immunoglobulin-like transcript 4-mediated functional inhibition of myelomonocytic cells. JOURNAL OF EXPERIMENTAL MEDICINE, 204 (12). 2813 - 2824 (12). ISSN 0022-1007 https://doi.org/10.1084/jem.20061865
SGUL Authors: Allen, Rachel Louise

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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

Item Type: Article
Additional Information: © 2007 Rockefeller University Press. Beginning six months after publication, RUP grants the public the non-exclusive right to copy, distribute, or display the Work under a Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/ and http://creativecommons.org/licenses/by-nc-sa/3.0/legalcode.
Keywords: Acquired Immunodeficiency Syndrome, CD8-Positive T-Lymphocytes, HIV, HIV Infections, HLA-B27 Antigen, Histocompatibility Antigens Class I, Humans, Monocytes, Mutation, Myeloid Cells, Receptors, Antigen, T-Cell, T-Lymphocytes, Cytotoxic, Science & Technology, Life Sciences & Biomedicine, Immunology, Medicine, Research & Experimental, Research & Experimental Medicine, CLASS-I MOLECULES, T-LYMPHOCYTE RESPONSE, VIRUS TYPE-1 INFECTION, NATURAL-KILLER-CELLS, DENDRITIC CELLS, HIV-1 INFECTION, IMMUNODEFICIENCY VIRUSES, IMMUNE ESCAPE, HOMOLOG UL18, CUTTING EDGE
SGUL Research Institute / Research Centre: Academic Structure > Infection and Immunity Research Institute (INII)
Journal or Publication Title: JOURNAL OF EXPERIMENTAL MEDICINE
ISSN: 0022-1007
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Dates:
DateEvent
26 November 2007Published
Web of Science ID: WOS:000251320300008
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URI: http://openaccess.sgul.ac.uk/id/eprint/1299
Publisher's version: https://doi.org/10.1084/jem.20061865

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