HLA-restricted epitope identification and detection of functional T cell responses by using MHC-peptide and costimulatory microarrays.
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.
Stone
Jennifer D
JD
Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
Demkowicz
Walter E
WE
Stern
Lawrence J
LJ
D017951:Antigen Presentation; D016207:Cytokines / Q000096:biosynthesis; D018984:Epitopes, T-Lymphocyte; D006680:HLA Antigens / Q000502:physiology*; D006801:Humans; D008213:Lymphocyte Activation; D040081:Protein Array Analysis; D013601:T-Lymphocytes / Q000276:immunology*
D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D006680:HLA Antigens
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