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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., 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.

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