HLA-restricted epitope identification and detection of functional T cell responses by using MHC–peptide and costimulatory microarrays

AUTOR(ES)

Stone, Jennifer D.

FONTE

National Academy of Sciences

RESUMO

Identification of T cell epitopes is a vital but often slow and difficult step in studying the immune response to infectious agents and autoantigens. We report a spatially addressable technique for screening large numbers of T cell epitopes for both specific antigen recognition and functional activity induced. This system uses microarrays of immobilized, recombinant MHC–peptide complexes, costimulatory molecules, and cytokine-capture antibodies. The array elements act as synthetic antigen-presenting cells and specifically elicit T cell responses, including adhesion, secretion of cytokines, and modulation of surface markers. The method allows facile identification of pertinent T cell epitopes in a large number of candidates and simultaneous determination of the functional outcome of the interaction. Using this method, we have characterized the activation of human CD4+ and CD8+ T cells responding to vaccinia, influenza, HIV-1, and Epstein–Barr viruses.

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