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Detection and Direct Stimulation of Antigen‐specific T cells by Nanometric Membrane Vesicles Expressing pMHC Complexes
Author(s) -
Kim Kwangmi,
Wang Lin,
Sprent Jonathan,
Hwang Inkyu
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.2_supplement.568
Subject(s) - vesicle , microbiology and biotechnology , t cell , immunological synapse , chemistry , antigen presenting cell , cell membrane , biophysics , antigen , cell , cytotoxic t cell , biology , immune system , in vitro , membrane , t cell receptor , biochemistry , immunology
Nanometric vesicles expressing cognate MHC/peptide complexes (pMHC) emerge as a powerful tool for eliciting antigen‐specific T cell immune response. Given the idea that productive T cell activation requires T cell contact with antigen presenting cells (APCs) on large cell surface forming immunological synapse prevails, full activation of T cells by the nano‐vesicles is quite surprising. Here, we show that the nano‐sized vesicles prepared from the plasma membrane of artificial APCs (Drosophila cell line S2 expressing various mouse immunomolecules), expressing less than 5–6 pMHCs, can trigger the TCRs to induce ′inside‐out′ signal for LFA‐1 activation, by which overall strength and stability of interaction between T cells and the vesicles expressing the pMHC plus ICAM‐1 are greatly promoted. We also show that the vesicles expressing a specific pMHC, along with ICAM‐1 and B7, can directly stimulate T cells recognizing the pMHC to undergo multiple cell divisions and acquire and effector functions both in vitro and in vivo . To facilitate handling and storage of the nano‐vesicles, we attempted to chemically fix the vesicles with paraformaldehyde (PFA) and found that the PFA‐fixed vesicles hold the greater potency for T cell activation than the unfixed natural vesicles. This finding implies a novel strategy for developing efficacious cell‐free T cell vaccines. This work was supported by NIH Grant R01AI066146.