A cytosolic pathway for MHC class II-restricted antigen processing that is proteasome and TAP dependent.
By convention, presentation of major histocompatibility complex (MHC) class I-restricted epitopes involves processing by cytosolic proteasomes, whereas MHC class II-restricted epitopes are generated by endosomal proteases. Here, we show that two MHC class II-restricted epitopes within influenza virus were generated by a proteasome- and TAP-dependent pathway that was accessed by exogenous virus in dendritic cells (DCs) but not cell types with less permeable endosomes. Both epitopes were presented by recycling MHC class II molecules. Challenging mice with influenza or vaccinia viruses demonstrated that a substantial portion of the MHC class II-restricted response was directed against proteasome-dependent epitopes. By complementing endosomal activities, this pathway broadens the array of MHC class II-restricted epitopes available for CD4(+) T cell activation.
Tewari
Mona K
MK
Department of Microbiology & Immunology, Kimmel Cancer Institute, Thomas Jefferson University, 233 S. 10th Street, BLSB 730, Philadelphia, Pennsylvania 19107, USA.
Sinnathamby
Gomathinayagam
G
Rajagopal
Deepa
D
Eisenlohr
Laurence C
LC
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters / Q000502:physiology*; D000818:Animals; D017951:Antigen Presentation; D003593:Cytoplasm / Q000378:metabolism*; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D051379:Mice; D046988:Proteasome Endopeptidase Complex / Q000502:physiology*; D015398:Signal Transduction
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; D000949:Histocompatibility Antigens Class II; C486171:Tap1 protein, mouse; D046988:Proteasome Endopeptidase Complex