Abstract
Transgenic 3.L2 T cells are stimulated by Hb(64-76)/I-Ek and are positively selected on I-Ek plus self-peptides. To this pool of self-peptides we have added a single, well-defined 3.L2 TCR antagonist (A72) in vivo. We find that mice expressing both the 3.L2 TCR and A72 have a minimal loss of T cells expressing the clonotypic TCR in the thymus and spleen. Importantly, the proliferative response of 3.L2 x A72 splenocytes is significantly reduced compared with splenocytes from 3.L2 mice. This reduced response can be attributed to peripheral antagonism. Thus we have identified a new class of self-ligands whose predominant effect is constitutive peripheral antagonism rather than negative selection. The net effect of these ligands is to avoid potential self-reactivity while maintaining as large a repertoire as possible.
Publication types
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Comparative Study
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Antigen-Presenting Cells / metabolism
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Chickens
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Clone Cells
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Hemoglobins / genetics
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Hemoglobins / immunology
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Hemoglobins / pharmacology*
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Histocompatibility Antigens Class II / immunology
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Immune Tolerance* / drug effects
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Ligands
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Lymphocyte Activation
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Lymphocyte Count
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Mice
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Mice, Inbred AKR
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Mice, Inbred C57BL
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Mice, Transgenic
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Muramidase / genetics
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Muramidase / immunology
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Peptide Fragments / genetics
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Peptide Fragments / immunology
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Peptide Fragments / pharmacology*
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Receptors, Antigen, T-Cell / antagonists & inhibitors*
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Receptors, Antigen, T-Cell / biosynthesis
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Recombinant Fusion Proteins / biosynthesis
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Recombinant Fusion Proteins / genetics
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Spleen / cytology
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Spleen / immunology
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Spleen / metabolism
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T-Lymphocyte Subsets / drug effects
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T-Lymphocyte Subsets / immunology*
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T-Lymphocyte Subsets / metabolism*
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Thymus Gland / cytology
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Thymus Gland / immunology
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Thymus Gland / metabolism
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Transgenes / immunology
Substances
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Hemoglobins
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Histocompatibility Antigens Class II
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Ligands
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Peptide Fragments
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Receptors, Antigen, T-Cell
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Recombinant Fusion Proteins
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hemoglobin (64-76)
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hen egg lysozyme peptide (46-61)
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Muramidase