Cutting Edge: Selective role of ubiquitin in MHC class I antigen presentation.
The importance of ubiquitination in MHC class I-restricted Ag processing remains unclear. To address this issue, we overexpressed wild-type and dominant-negative lysineless forms of ubiquitin (Ub) in mammalian cells using an inducible vaccinia virus system. Overexpression of the lysineless Ub nearly abrogated polyubiquitination and potently inhibited epitope presentation from a cytosolic N-end rule substrate as well as endoplasmic reticulum (ER)-targeted model Ags. In contrast, there was little impact on Ag presentation from cytosolic proteins. These trends were location dependent; redirecting cytosolic Ag to the ER rendered presentation lysineless Ub-sensitive, whereas retargeting exocytic Ag to the cytosol had the inverse effect. This dichotomy was further underscored by small interfering RNA knockdown of the ER-associated Ub ligase Hrd1. Thus, Ub-dependent degradation appears to play a major role in the MHC class I-restricted processing of ER-targeted proteins and a more restricted role in the processing of cytosolic proteins.
Department of Microbiology and Immunology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Lan
L
Huang
Julie M
JM
Marvin
Nia
N
Tatsis
Laurence C
LC
Eisenlohr
D000818:Animals; D017951:Antigen Presentation / Q000235:genetics / Q000276:immunology*; D002645:Chickens; D006183:H-2 Antigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D010047:Ovalbumin / Q000276:immunology / Q000378:metabolism; D010455:Peptides / Q000276:immunology / Q000378:metabolism; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics; D054875:Ubiquitination; D014452:Ubiquitins / Q000235:genetics / Q000502:physiology*; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology
D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; D015395:Histocompatibility Antigens Class I; D010455:Peptides; D011994:Recombinant Proteins; D014452:Ubiquitins; D010047:Ovalbumin
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