Myeloid differentiation factor 88 is required for cross-priming in vivo.
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.
Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Deborah
D
Palliser
Hidde
H
Ploegh
Marianne
M
Boes
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D017951:Antigen Presentation / Q000235:genetics; D000942:Antigens, Bacterial / Q000008:administration & dosage / Q000378:metabolism; D000943:Antigens, Differentiation / Q000235:genetics / Q000502:physiology*; D001426:Bacterial Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D018834:Chaperonin 60; D018833:Chaperonins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D007114:Immunization / Q000379:methods; D007279:Injections, Subcutaneous; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009169:Mycobacterium tuberculosis / Q000276:immunology; D053594:Myeloid Differentiation Factor 88; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism; D011971:Receptors, Immunologic / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000276:immunology / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism / Q000637:transplantation; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D048868:Adaptor Proteins, Signal Transducing; D000942:Antigens, Bacterial; D000943:Antigens, Differentiation; D001426:Bacterial Proteins; D018834:Chaperonin 60; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D010446:Peptide Fragments; D011971:Receptors, Immunologic; D011993:Recombinant Fusion Proteins; C074119:heat-shock protein 65, Mycobacterium; D018833:Chaperonins