Abstract
Most current models of T cell activation postulate a requirement for two distinct signals. One signal is delivered through the TCR by engagement with peptide/MHC complexes, and the second is delivered by interaction between costimulatory molecules such as CD28 and its ligands CD80 and CD86. Soluble peptide/MHC tetramers provide an opportunity to test whether naive CD8+ T cells can be activated via the signal generated through the TCR-alphabeta in the absence of any potential costimulatory molecules. Using T cells from two different TCR transgenic mice in vitro, we find that TCR engagement by peptide/MHC tetramers is sufficient for the activation of naive CD8+ T cells. Furthermore, these T cells proliferate, produce cytokines, and differentiate into cytolytic effectors. Under the conditions where anti-CD28 is able to enhance proliferation of normal B6 CD4+, CD8+, and TCR transgenic CD8+ T cells with anti-CD3, we see no effect of anti-CD28 on proliferation induced by tetramers. The results of this experiment argue that given a strong signal delivered through the TCR by an authentic ligand, no costimulation is required.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Antigens, Viral*
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CD8 Antigens / metabolism
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CD8-Positive T-Lymphocytes / cytology*
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CD8-Positive T-Lymphocytes / immunology*
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CD8-Positive T-Lymphocytes / metabolism
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Cell Differentiation / genetics
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Cell Differentiation / immunology
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Cell Separation
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Glycoproteins / immunology
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H-Y Antigen / immunology
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Histocompatibility Antigens Class I / metabolism
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Immunophenotyping
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Interphase / genetics
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Interphase / immunology
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Lymphocyte Activation / genetics
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Lymphocyte Activation / immunology*
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Lymphocytic choriomeningitis virus / immunology
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Male
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Mice
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Mice, Inbred C57BL
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Mice, Transgenic
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Peptide Fragments / immunology
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Receptors, Antigen, T-Cell / genetics
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Receptors, Antigen, T-Cell / physiology
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Signal Transduction / immunology
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T-Lymphocyte Subsets / cytology*
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T-Lymphocyte Subsets / immunology*
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T-Lymphocyte Subsets / metabolism
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T-Lymphocytes, Cytotoxic / cytology*
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T-Lymphocytes, Cytotoxic / immunology*
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T-Lymphocytes, Cytotoxic / metabolism
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Viral Proteins*
Substances
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Antigens, Viral
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CD8 Antigens
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Glycoproteins
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H-Y Antigen
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Histocompatibility Antigens Class I
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Peptide Fragments
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Receptors, Antigen, T-Cell
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Viral Proteins
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glycoprotein peptide 33-41, Lymphocytic choriomeningitis virus