Peptide-receptive major histocompatibility complex class I molecules cycle between endoplasmic reticulum and cis-Golgi in wild-type lymphocytes.
Prior to binding to a high affinity peptide and transporting it to the cell surface, major histocompatibility complex class I molecules are retained inside the cell by retention in the endoplasmic reticulum (ER), recycling through the ER-Golgi intermediate compartment and possibly the cis-Golgi, or both. Using fluorescence microscopy and a novel in vitro COPII (ER-to-ER-Golgi intermediate compartment) vesicle formation assay, we find that in both lymphocytes and fibroblasts that lack the functional transporter associated with antigen presentation, class I molecules exit the ER and reach the cis-Golgi. Intriguingly, in wild-type T1 lymphoma cells, peptide-occupied and peptide-receptive class I molecules are simultaneously exported from ER membranes with similar efficiencies. Our results suggest that binding of high affinity peptide and exit from the ER are not coupled, that the major histocompatibility complex class I quality control compartment extends into the Golgi apparatus under standard conditions, and that peptide loading onto class I molecules may occur in post-ER compartments.
Biochemistry and Cell Biology, School of Engineering and Science, Jacobs University Bremen, 28759 Bremen, Germany.
Malgorzata
M
Garstka
Britta
B
Borchert
Mohammed
M
Al-Balushi
P V K
PV
Praveen
Nicole
N
Kühl
Irina
I
Majoul
Rainer
R
Duden
Sebastian
S
Springer
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D016466:CHO Cells; D022181:COP-Coated Vesicles / Q000276:immunology / Q000378:metabolism; D002522:Chlorocebus aethiops; D006224:Cricetinae; D003412:Cricetulus; D004721:Endoplasmic Reticulum / Q000276:immunology* / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D006056:Golgi Apparatus / Q000276:immunology* / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D008214:Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D051379:Mice; D010455:Peptides / Q000276:immunology* / Q000378:metabolism; D021381:Protein Transport; D014709:Vero Cells
D015395:Histocompatibility Antigens Class I; D010455:Peptides