PURIFIED MHC CLASS-I AND PEPTIDE COMPLEXES ACTIVATE NAIVE CD8(-CELLS INDEPENDENTLY OF THE CD28() T)B7 AND LFA-1/ICAM-1 COSTIMULATORY INTERACTIONS/

T cells play a central role in the initiation, maintenance, and regula tion of the immune response. Effector responses of T cells are control led by complex combinations of lymphokines and adhesion/costimulatory molecule signals. To isolate the effects of specific adhesion/costimul atory molecules and to define the minimal molecular requirements of na ive CD8(+) T cell activation, we have developed an APC-free system for stimulation of naive CD8(+) T cells. In this report, we demonstrate t hat immobilized MHC class I-peptide complexes can activate naive CD8() T cells from TCR transgenic mice at low cell densities. The CD8(+) T cells were stimulated to proliferate and secrete IL-2 independently o f the molecular interactions between CD28/B7.1-B7.2 or LFA-1/ICAM-1 su rface receptors. Previous reports have shown that CD28 ligation is nec essary for late T cell survival of APC-stimulated naive CD8(+) T cells . Our data suggest that under certain specific conditions of high inte nsity T cell signaling, early activation and late cell proliferation c an occur independently of APC-derived costimulatory signals.