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Stimulation of HIV-specific T cell clonotypes using allogeneic HLA

Almeida, C., van Miert, P., O'Driscoll, K., Zoet, Y.M., Chopra, A., Watson, M.ORCID: 0000-0002-6438-9225, de Santis, D., Witt, C., John, M., Claas, F.H.J. and D'Orsogna, L.J. (2017) Stimulation of HIV-specific T cell clonotypes using allogeneic HLA. Cellular Immunology, 316 . pp. 32-40.

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We hypothesized that HIV-specific CD8 T cell clonotypes can be stimulated by allogeneic HLA molecules. Multiple HIV-specific CD8 T cell clones were derived from 12 individuals with chronic HIV infection, specific for 13 different HIV Gag antigens and restricted to 7 different HLA molecules. The generated T cell clones were assayed for alloreactivity against a panel of single HLA class I expressing cell lines (SALs). HIV-specific T cells recognising at least one allogeneic HLA molecule could be identified from 7 of 12 patients tested. Allorecognition was associated with IFNγ cytokine production, CD137 upregulation and cytotoxicity, suggesting high avidity allo-stimulation. Allo-HLA recognition by HIV-specific T cells was specific to the HIV target peptide/HLA restriction and TCR TRBV usage of the T cells. HIV-specific T cells do crossreact against allogeneic HLA molecules in an epitope and TRBV specific manner. Therefore allo-HLA stimulation could be exploited to induce or augment HIV-specific T cell responses.

Item Type: Journal Article
Murdoch Affiliation(s): Institute for Immunology and Infectious Diseases
Publisher: Academic Press Inc.
Copyright: © 2017 Elsevier Inc.
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