ABSTRACT
T cells play a central role in the initiation, maintenance, and regulation of the immune response. Effector responses of T cells are controlled by complex combinations of lymphokines and adhesion/costimulatory molecule signals. To isolate the effects of specific adhesion/costimulatory molecules and to define the minimal molecular requirements of naive CD8+ T cell activation, we have developed an APC-free system for stimulation of naive CD8+ T cells. In this report, we demonstrate that 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 of the molecular interactions between CD28/B7.1-B7.2 or LFA-1/ICAM-1 surface receptors. Previous reports have shown that CD28 ligation is necessary for late T cell survival of APC-stimulated naive CD8+ T cells. Our data suggest that under certain specific conditions of high intensity T cell signaling, early activation and late cell proliferation can occur independently of APC-derived costimulatory signals.
Subject(s)
B7-1 Antigen/physiology , CD28 Antigens/physiology , CD8-Positive T-Lymphocytes/immunology , Histocompatibility Antigens Class I/physiology , Intercellular Adhesion Molecule-1/physiology , Lymphocyte Activation , Lymphocyte Function-Associated Antigen-1/physiology , Oligopeptides/immunology , Animals , CD8-Positive T-Lymphocytes/metabolism , Female , Histocompatibility Antigens Class I/isolation & purification , Interleukin-2/metabolism , Interphase/immunology , Lymphocyte Activation/drug effects , Lymphocyte Count , Mice , Mice, Inbred C57BL , Mice, Transgenic , Oligopeptides/isolation & purification , Oligopeptides/pharmacology , Receptors, Antigen, T-Cell/geneticsABSTRACT
In this report, we demonstrate stimulation of T cell receptor (TCR) transgenic CD8 T cells by isolated major histocompatibility complex (MHC) class I H-2Ld complexes and antigenic peptide. This is the first demonstration of CD8 T cells activated by MHC and antigenic peptide in the absence of antigen priming. Furthermore, isolated MHC and a potent peptide antigen can stimulate phenotypically naive CD44- T cells to become CTL effectors and to produce interleukin-2 in nanogram per milliliter amounts. These results demonstrate that particular TCR antigen pairs may overcome the need for specialized antigen-presenting cells and have implications for mechanisms of autoimmunity and tolerance induction.