Peptide diffusion, protection, and degradation in nuclear and cytoplasmic compartments before antigen presentation by MHC class I.
Antigenic peptides generated by the proteasome have to survive a peptidase-containing environment for presentation by MHC class I molecules. We have visualized the fate and dynamics of intracellular peptides in living cells. We show that peptides are distributed over two different but interconnected compartments, the cytoplasm and the nucleus, and diffuse rapidly through and between these compartments. Since TAP is excluded from the nuclear face of the nuclear envelope, nuclear peptides have to leave the nucleus to contact TAP. Thereby, these peptides encounter cytosolic peptidases that degrade peptides within seconds unless bound to chromatin. Since peptide degradation is far more efficient than translocation, many peptides will be lost for antigen presentation by MHC class I molecules.
Reits
Eric
E
Department of Tumor Biology and Cell Biology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
Griekspoor
Alexander
A
Neijssen
Joost
J
Groothuis
Tom
T
Jalink
Kees
K
van Veelen
Peter
P
Janssen
Hans
H
Calafat
Jero
J
Drijfhout
Jan Wouter
JW
Neefjes
Jacques
J
D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000595:Amino Acid Sequence; D017951:Antigen Presentation; D002451:Cell Compartmentation; D002460:Cell Line; D002467:Cell Nucleus / Q000276:immunology / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000378:metabolism; D003593:Cytoplasm / Q000276:immunology / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000276:immunology / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D016253:Microscopy, Immunoelectron; D009097:Multienzyme Complexes / Q000378:metabolism; D010455:Peptides / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex; D011485:Protein Binding
D018528:ATP-Binding Cassette Transporters; D015395:Histocompatibility Antigens Class I; D009097:Multienzyme Complexes; D010455:Peptides; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex