Restoration of antigen presentation to the mutant cell line RMA-S by an MHC-linked transporter.
In mammalian cells, short peptides derived from intracellular proteins are displayed on the cell membrane associated with class I molecules of the major histocompatibility complex (MHC). The surface presentation of class I-peptide complexes presumably alerts the immune system to intracellular viral protein synthesis. Peptides derived from the cytosol must reach the cisternae of the endoplasmic reticulum where they are required for the assembly of stable class I molecules, and it has been proposed that the products of the two MHC-encoded ATP-binding cassette (ABC) transporter genes function to deliver the peptides across the membrane of the endoplasmic reticulum. This idea is supported by experiments in which transfection of a human cell line defective in class I expression with a complementary DNA of one of these genes restored cell surface expression levels. Here we show that the complete phenotype of the mouse mutant cell line RMA-S, in which lack of surface expression of stable class I molecules correlates with an inability to present viral peptides originating in the cytosol, is repaired by the cDNA of the other transporter gene. These results are consistent with the possibility that the two transporter polypeptides form a heterodimer.
Powis
S J
SJ
Department of Immunology, AFRC Institute of Animal Physiology and Genetics Research, Babraham, Cambridge, UK.
Townsend
A R
AR
Deverson
E V
EV
Bastin
J
J
Butcher
G W
GW
Howard
J C
JC
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; D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D002460:Cell Line; D002478:Cells, Cultured; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D005434:Flow Cytometry; D015723:Gene Library; D005805:Genes, MHC Class I; D000949:Histocompatibility Antigens Class II; D006801:Humans; D007700:Kinetics; D008285:Major Histocompatibility Complex; D008565:Membrane Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D011487:Protein Conformation; D051381:Rats; D015183:Restriction Mapping; D012689:Sequence Homology, Nucleic Acid
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; D000949:Histocompatibility Antigens Class II; D008565:Membrane Proteins; C073119:TAP1 protein, human; C486172:Tap1 protein, rat; C489516:Tap2 protein, mouse; C489514:Tap2 protein, rat; C071692:TAP2 protein, human; D004247:DNA