TAP mediates import of Mycobacterium tuberculosis-derived peptides into phagosomes and facilitates loading onto HLA-I.
Processing and presentation of antigen on MHC-I class I molecules serves to present peptides derived from cytosolic proteins to CD8(+) T cells. Infection with bacteria that remain in phagosomal compartments, such as Mycobacterium tuberculosis (Mtb), provides a challenge to this immune recognition as bacterial proteins are segregated from the cytosol. Previously we identified the Mtb phagosome itself as an organelle capable of loading MHC Class I molecules with Mtb antigens. Here, we find that the TAP transporter, responsible for importing peptides into the ER for loading in Class I molecules, is both present and functional in Mtb phagosomes. Furthermore, we describe a novel peptide reagent, representing the N-terminal domain of the bovine herpes virus UL49.5 protein, which is capable of specifically inhibiting the lumenal face of TAP. Together, these results provide insight into the mechanism by which peptides from intra-phagosomal pathogens are loaded onto Class I molecules.
Portland VA Medical Center, Portland, Oregon, United States of America ; Department of Pulmonary and Critical Care Medicine, Oregon Health & Sciences University, Portland, Oregon, United States of America.
Melanie J
MJ
Harriff
Sven
S
Burgdorf
Christian
C
Kurts
Emmanuel J H J
EJ
Wiertz
Deborah A
DA
Lewinsohn
David M
DM
Lewinsohn
D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects / Q000276:immunology; D000942:Antigens, Bacterial / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D051379:Mice; D009169:Mycobacterium tuberculosis / Q000276:immunology / Q000378:metabolism*; D010455:Peptides / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D010588:Phagosomes / Q000378:metabolism*; D021381:Protein Transport
D018528:ATP-Binding Cassette Transporters; D000942:Antigens, Bacterial; D015395:Histocompatibility Antigens Class I; D010455:Peptides; C477327:transporter associated with antigen processing (TAP)