PROBING THE ACTIVATION REQUIREMENTS FOR NAIVE CD8(-CELLS WITH DROSOPHILA CELL TRANSFECTANTS AS ANTIGEN-PRESENTING CELLS() T)

Activation of T cells involves multiple receptor-ligand interactions b etween T cells and antigen presenting cells (APC). At least two signal s are required for T-cell activation: Signal 1 results from recognitio n of MHC/peptide complexes on the APC by cell surface T-cell receptors (TCR), whereas Signal 2 is induced by the interactions of co-stimulat ory molecules on APC with their complementary receptors on T cells. Th is 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 alo ne and in complex with MHC/peptide. Analysis of these structures has p rovided some basic rules for how TCR and MHC/peptide interact; however , the critical question of how this interaction transduces Signal 1 to T cells remains unclear. The effects of Signal 1 and Signal 2 on T-ce ll activation were examined with naive T cells from the 2C TCR transge nic mice, defined peptides as antigen and transfected Drosophila cells as APC. The results suggest that, except under extreme conditions, Si gnal 1 alone is unable to activate naive CD8 T cells despite the induc tion of marked TCR downregulation. Either B7 or intercellular adhesion molecule (ICAM)-1 can provide the second signal for CD8 T-cell activa tion. However, especially at low MHC/peptide densities, optimal activa tion and differentiation of CD8 T cells required interaction with both B7 and ICAM-1 on the same APC. Thus, the data suggest that at least t wo qualitatively different co-stimulation signals are required for ful l activation of CD8 T cells under physiological conditions.