Ex vivo characterization of allo-MHC-restricted T cells specific for a single MHC-peptide complex |
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Authors: | Pittet Mikaël J Gati Asma Le Gal Frederic-Anne Bioley Gilles Guillaume Philippe de Smedt Magda Plum Jean Speiser Daniel E Cerottini Jean-Charles Dietrich Pierre-Yves Romero Pedro Zippelius Alfred |
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Institution: | Division of Clinical Onco-Immunology, Ludwig Institute for Cancer Research, University Hospital, Lausanne, Switzerland. |
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Abstract: | Alloreactive T cells are thought to be a potentially rich source of high-avidity T cells with therapeutic potential since tolerance to self-Ags is restricted to self-MHC recognition. Given the particularly high frequency of alloreactive T cells in the peripheral immune system, we used numerous MHC class I multimers to directly visualize and isolate viral and tumor Ag-specific alloreactive CD8 T cells. In fact, all but one specificities screened were undetectable in ex vivo labeling. In this study, we report the occurrence of CD8 T cells specifically labeled with allo-HLA-A*0201/Melan-A/MART-1(26-35) multimers at frequencies that are in the range of 10(-4) CD8 T cells and are thus detectable ex vivo by flow cytometry. We report the thymic generation and shaping of tumor Ag-specific, alloreactive T cells as well as their fate once seeded in the periphery. We show that these cells resemble their counterparts in HLA-A*0201-positive individuals, based on their structural and functional attributes. |
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