Abstract
The improved efficacy of high avidity CTL for clearance of virus has been well-documented. Thus, elucidation of the mechanisms that confer the increased sensitivity to peptide ligand demonstrated by high avidity CTL is critical. Using CTL lines of high and low avidity generated from a TCR transgenic mouse, we have found that functional avidity can be controlled by the expression of CD8alphaalpha vs CD8alphabeta and the ability of CTLs to colocalize the TCR and CD8 in the membrane. Colocalization of these molecules was mediated by lipid rafts and importantly, raft disruption resulted in the conversion of high avidity CTL into a lower functional avidity phenotype. These novel findings provide insights into the control of functional avidity in response to viral infection.
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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CD8 Antigens / biosynthesis
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CD8 Antigens / metabolism*
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CD8 Antigens / physiology
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Cell Line
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Coculture Techniques
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Cytotoxicity, Immunologic*
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Immunophenotyping
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Lymphocyte Activation
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Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / biosynthesis
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Membrane Microdomains / immunology
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Membrane Microdomains / metabolism
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Mice
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Mice, Inbred C57BL
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Mice, Transgenic
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Receptors, Antigen, T-Cell / genetics
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Receptors, Antigen, T-Cell / metabolism*
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Receptors, Antigen, T-Cell / physiology
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T-Lymphocytes, Cytotoxic / enzymology
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T-Lymphocytes, Cytotoxic / immunology*
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T-Lymphocytes, Cytotoxic / metabolism*
Substances
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CD8 Antigens
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Receptors, Antigen, T-Cell
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Lymphocyte Specific Protein Tyrosine Kinase p56(lck)