Abstract
The interactions between CD28 and its ligand CD86 are critical for the regulation of T cell responses. However, it is not clear whether CD4+ T cells expressing low and high avidity TCR are equally dependent on CD28 costimulation for their activation and expansion. To address this issue, we have used multimers of I-Ad molecules linked to a peptide derived from the Leishmania major homolog for the receptor of activated C kinase (LACK) antigen to compare the fate of LACK-specific CD4+ T cells in Leishmania-infected BALB/c mice which have been treated or not with anti-CD86 mAb. Although the administration of anti-CD86 mAb did not completely prevent the expansion of LACK-specific T cells, their frequency and number were markedly reduced. In mice treated with anti-CD86 mAb as well as in control animals, L. major induced the clonal expansion of LACK-specific T cells which expressed a canonical low avidity Valpha8/Vbeta4 TCR. Taken together, our results suggest that the molecular interactions between CD28 on T cells and CD86 on APC serve to amplify and modulate T cell responses without promoting breadth in the TCR repertoire.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antibodies, Monoclonal / pharmacology
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Antigens, CD / immunology
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Antigens, Protozoan
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B7-2 Antigen
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CD4-Positive T-Lymphocytes / immunology*
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Female
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Genes, T-Cell Receptor beta
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Histocompatibility Antigens Class II / metabolism
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Leishmania major* / immunology
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Leishmaniasis, Cutaneous / immunology*
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Male
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Membrane Glycoproteins / antagonists & inhibitors*
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Membrane Glycoproteins / immunology
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Mice
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Mice, Inbred BALB C
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Mice, Transgenic
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Protozoan Proteins / immunology
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Receptors, Nerve Growth Factor / immunology
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Receptors, OX40
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Receptors, Tumor Necrosis Factor / immunology
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Tumor Necrosis Factor Receptor Superfamily, Member 7 / metabolism
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Tumor Necrosis Factor Receptor Superfamily, Member 9
Substances
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Antibodies, Monoclonal
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Antigens, CD
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Antigens, Protozoan
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B7-2 Antigen
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Cd86 protein, mouse
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Histocompatibility Antigens Class II
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I-Ad antigen
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Membrane Glycoproteins
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Protozoan Proteins
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Receptors, Nerve Growth Factor
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Receptors, OX40
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Receptors, Tumor Necrosis Factor
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Tnfrsf4 protein, mouse
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Tnfrsf9 protein, mouse
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Tumor Necrosis Factor Receptor Superfamily, Member 7
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Tumor Necrosis Factor Receptor Superfamily, Member 9
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LACK antigen, Leishmania