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Probing the activation requirements for naive CD8 + T cells with Drosophila cell transfectants as antigen presenting cells
Author(s) -
Cai Zeling,
Brunmark Anders B.,
Luxembourg Alain T,
Garcia K. Christopher,
Degano Massimo,
Teyton Luc,
Wilson Ian,
Peterson Per A.,
Sprent Jonathan,
Jackson Michael R.
Publication year - 1998
Publication title -
immunological reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.839
H-Index - 223
eISSN - 1600-065X
pISSN - 0105-2896
DOI - 10.1111/j.1600-065x.1998.tb01243.x
Subject(s) - biology , antigen , antigen presenting cell , microbiology and biotechnology , cytotoxic t cell , cd8 , drosophila (subgenus) , t cell , transfection , immunology , cell culture , genetics , gene , immune system , in vitro
Summary: Activation of T cells involves multiple receptor‐ligand interactions between T cells and antigen presenting cells (APC), At least two signals are required for T‐cell activation: Signal 1 results from recognition of MHC/peptide complexes on the APC by cell surface T‐cell receptors (TCR). whereas Signal 2 is induced by the interactions of co‐stimulatory molecules on APC with their complementary receptors on T cells. This review focuses on our attempts to understand these various signals in a model system involving the 2C TCR. The structural basis of Signal 1 was investigated by determining the crystal structure of 2C TCR alone and in complex with MHC/peptide. Analysis of these structures has provided some basic rules for how TCR and MHC/peptide interact; however, the critical question of how this interaction transduces Signal I to T cells remains unclear. The effects of Signal 1 and Signal 2 on T‐cell activation were examined with naive T cells from the 2C TCR transgenic mice, defined peptides as antigen and transfected Drosophila cells as APC. The results suggest that, except under extreme conditions, Signal I alone is unable to activate naive CD8 T cells despite the induction of marked TCR downregulation. Either B7 or intercellular adhesion molecule (ICAM)‐l can provide the second signal for CD8 T‐cell activation. However, especially at low MHC/peptide densities, optimal activation and differentiation of CD8 T cells required interaction with both B7 and [CAM‐1 on the same APC. Thus, the data suggest that at least two qualitatively different co‐stimulation signals are required for full activation of CD8 T cells under physiological conditions.