Location of MHC-encoded transporters in the endoplasmic reticulum and cis-Golgi.
Immune recognition of intracellular proteins is mediated by major histocompatibility complex (MHC) class I molecules that present short peptides to cytotoxic T cells. Evidence suggests that peptides arise by cleavage of proteins in the cytoplasm and are transported by a signal-independent mechanism into a pre-Golgi region of the cell, where they take part in the assembly of class I heavy chains with beta 2-microglobulin (reviewed in refs 5-7). Analysis of cells that have defects in class I molecule assembly and antigen presentation has shown that this phenotype can result from mutations in either of the two ABC transporter genes located in the class II region of the MHC. This suggested that the protein complex encoded by these two genes transports peptides from the cytosol into the endoplasmic reticulum. Here we report additional evidence by showing that the transporter complex is located in the endoplasmic reticulum membrane and is probably oriented with its ATP-binding domains in the cytosol.
Kleijmeer
M J
MJ
Department of Cell Biology, School of Medicine, University of Utrecht, The Netherlands.
Kelly
A
A
Geuze
H J
HJ
Slot
J W
JW
Townsend
A
A
Trowsdale
J
J
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters; D000595:Amino Acid Sequence; D001665:Binding Sites; D001692:Biological Transport; D002352:Carrier Proteins / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000737:chemistry* / Q000378:metabolism; D006056:Golgi Apparatus / Q000737:chemistry* / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000032:analysis / Q000378:metabolism; D008285:Major Histocompatibility Complex; D008565:Membrane Proteins / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D016296:Mutagenesis; D010455:Peptides / Q000276:immunology / Q000378:metabolism; D014162:Transfection
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters; D002352:Carrier Proteins; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D010455:Peptides; C073119:TAP1 protein, human; C071692:TAP2 protein, human