Abstract
We describe a role for myeloid differentiation factor 88 (MyD88) in the induction of functional CTLs in vivo, in response to exogenously administered Ag, using a heat shock fusion protein, hsp65-P1, as a model Ag. CD8 T cells transferred into MyD88-deficient animals produce normal numbers of CD8 effector cells that have normal activation marker profiles after immunization with hsp65-P1. However, these CD8 T cells produced significantly less IFN-gamma and showed reduced killing activity. This reduction in activation of functional CTLs appears to be unrelated to Toll-like receptor 4 function, because in vitro hsp65-P1-experienced Toll-like receptor 4-deficient dendritic cells (DCs), but not MyD88-deficient DCs, activated CD8 T cells to a similar extent to wild-type DCs. We identify a cross-presentation defect in MyD88-deficient DCs that, when treated with hsp65-P1 fusion protein, results in surface display of fewer SIYRYYGL/class I MHC complexes. Thus, MyD88 plays a role in the developmental maturation of DCs that allows them to prime CD8 T cells through cross-presentation.
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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Adaptor Proteins, Signal Transducing
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Animals
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Antigen Presentation* / genetics
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Antigens, Bacterial / administration & dosage
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Antigens, Bacterial / metabolism
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Antigens, Differentiation / genetics
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Antigens, Differentiation / physiology*
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Bacterial Proteins / administration & dosage
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Bacterial Proteins / genetics
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Bacterial Proteins / immunology
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Bacterial Proteins / metabolism
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Cell Differentiation / genetics
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Cell Differentiation / immunology
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Cells, Cultured
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Chaperonin 60
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Chaperonins / administration & dosage
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Chaperonins / genetics
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Chaperonins / immunology
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Chaperonins / metabolism
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Cytotoxicity, Immunologic* / genetics
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Dendritic Cells / cytology
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Dendritic Cells / immunology
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Dendritic Cells / metabolism
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Immunization* / methods
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Injections, Subcutaneous
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Lymphocyte Activation / genetics
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Mice, Transgenic
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Mycobacterium tuberculosis / immunology
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Myeloid Differentiation Factor 88
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Peptide Fragments / immunology
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Peptide Fragments / metabolism
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Receptors, Immunologic / deficiency
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Receptors, Immunologic / genetics
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Receptors, Immunologic / physiology*
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Recombinant Fusion Proteins / administration & dosage
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Recombinant Fusion Proteins / immunology
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Recombinant Fusion Proteins / metabolism
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T-Lymphocyte Subsets / immunology
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T-Lymphocyte Subsets / metabolism
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T-Lymphocyte Subsets / transplantation
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T-Lymphocytes, Cytotoxic / immunology*
Substances
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Adaptor Proteins, Signal Transducing
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Antigens, Bacterial
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Antigens, Differentiation
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Bacterial Proteins
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Chaperonin 60
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Myd88 protein, mouse
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Myeloid Differentiation Factor 88
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Peptide Fragments
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Receptors, Immunologic
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Recombinant Fusion Proteins
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heat-shock protein 65, Mycobacterium
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Chaperonins