Assembly and function of the two ABC transporter proteins encoded in the human major histocompatibility complex.
Presentation of cytoplasmic antigens to class I-restricted cytotoxic T cells implied the existence of a specialized peptide transporter. For most class I heavy chains, association with peptides of the appropriate length is required for stable assembly with beta 2-microglobulin. Mutant cells RMA-S and .174/T2 neither assemble stable class I molecules nor present intracellular antigens, and we have suggested that they have lost a function required for the transport of short peptides from the cytosol to the endoplasmic reticulum. The genetic defect in .174 has been localized to a large deletion in the class II region of the major histocompatibility complex, within which two genes (RING4 and RING11) have been identified that code for 'ABC' (ATP-binding cassette) transporters. We report here that the protein products of these two genes assemble to form a complex. Defects in either protein result in the formation of unstable class I molecules and loss of presentation of intracellular antigens. The molecular defect in a new mutant, BM36.1, is shown to be in the ATP-binding domain of the RING11/PSF2 protein. This is in contrast to the mutant .134, which lacks the RING4/PSF1 protein.
Kelly
A
A
Imperial Cancer Research Fund, Lincoln's Inn Fields, London, UK.
Powis
S H
SH
Kerr
L A
LA
Mockridge
I
I
Elliott
T
T
Bastin
J
J
Uchanska-Ziegler
B
B
Ziegler
A
A
Trowsdale
J
J
Townsend
A
A
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; D000595:Amino Acid Sequence; D001483:Base Sequence; D015139:Blotting, Southern; D002352:Carrier Proteins / Q000502:physiology*; D004591:Electrophoresis, Polyacrylamide Gel; D015870:Gene Expression; D005838:Genotype; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis; D006801:Humans; D008285:Major Histocompatibility Complex / Q000235:genetics*; D008565:Membrane Proteins / Q000502:physiology*; D008969:Molecular Sequence Data; D009154:Mutation; D011233:Precipitin Tests; D014176:Protein Biosynthesis; D014170:Transformation, Genetic
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; D002352:Carrier Proteins; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; C073119:TAP1 protein, human