Purified MHC class I and peptide complexes activate naive CD8+ T cells independently of the CD28/B7 and LFA-1/ICAM-1 costimulatory interactions.
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.
Goldstein
J S
JS
Division of Monoclonal Antibodies, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA. goldstein@a1.cber.fda.gov
Chen
T
T
Brunswick
M
M
Mostowsky
H
H
Kozlowski
S
S
D000818:Animals; D018122:B7-1 Antigen / Q000502:physiology*; D018106:CD28 Antigens / Q000502:physiology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000302:isolation & purification / Q000502:physiology*; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology*; D007376:Interleukin-2 / Q000378:metabolism; D007399:Interphase / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D018655:Lymphocyte Count; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009842:Oligopeptides / Q000276:immunology* / Q000302:isolation & purification / Q000494:pharmacology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics
D018122:B7-1 Antigen; D018106:CD28 Antigens; D015395:Histocompatibility Antigens Class I; D007376:Interleukin-2; D016169:Lymphocyte Function-Associated Antigen-1; D009842:Oligopeptides; D011948:Receptors, Antigen, T-Cell; D018799:Intercellular Adhesion Molecule-1