Abstract
The thymus leukemia antigen (TL) is a nonclassical class I molecule, expressed abundantly on intestinal epithelial cells. We show that, in contrast to other major histocompatibility complex (MHC) class I molecules that bind CD8alphabeta, TL preferentially binds the homotypic form of CD8alpha (CD8alphaalpha). Thus, TL tetramers react specifically to CD8alphaalpha-expressing cells, including most intestinal intraepithelial lymphocytes. Compared with CD8alphabeta, which recognizes the same MHC as the T cell receptor (TCR) and thus acts as a TCR coreceptor, high-affinity binding of CD8alphaalpha to TL modifies responses mediated by TCR recognition of antigen presented by distinct MHC molecules. These findings define a novel mechanism of lymphocyte regulation through CD8alphaalpha and MHC class I.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Motifs
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Animals
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Antigen Presentation
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CD8 Antigens / genetics
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CD8 Antigens / immunology
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CD8 Antigens / metabolism*
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CD8-Positive T-Lymphocytes / immunology
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CD8-Positive T-Lymphocytes / metabolism
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Enterocytes / immunology
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Enterocytes / metabolism*
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Enzyme-Linked Immunosorbent Assay
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Flow Cytometry
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Gene Deletion
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H-2 Antigens / immunology
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H-2 Antigens / metabolism*
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Male
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Membrane Glycoproteins / chemistry
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Membrane Glycoproteins / immunology
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Membrane Glycoproteins / metabolism*
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Mice
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Mice, Inbred C57BL
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Mice, Transgenic
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Protein Interaction Mapping
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Protein Structure, Tertiary
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Receptors, Antigen, T-Cell / metabolism
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Substrate Specificity
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Surface Plasmon Resonance
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Tumor Cells, Cultured
Substances
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CD8 Antigens
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CD8 antigen, alpha chain
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H-2 Antigens
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Membrane Glycoproteins
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Receptors, Antigen, T-Cell
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thymus-leukemia antigens