Assembly and function of the two ABC transporter proteins encoded in the human major histocompatibility complex

• Published in: Nature (London) 1992-02, Vol.355 (6361), p.641-644
• Main Authors: Kelly, Adrian, Powis, Stephen H, Kerr, Lesley-Anne, Mockridge, Ian, Elliott, Timothy, Bastin, Judy, Uchanska-Ziegler, Barbara, Ziegler, Andreas, Trowsdale, John, Townsend, Alain
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; antigen presentation; ATP; ATP-Binding Cassette Sub-Family B Member 2; ATP-Binding Cassette Transporters; Base Sequence; Biochemistry; Blotting, Southern; Carrier Proteins - physiology; Cellular biology; Electrophoresis, Polyacrylamide Gel; endoplasmic reticulum; Gene Expression; Genotype; Histocompatibility Antigens Class I - biosynthesis; Humanities and Social Sciences; Humans; letter; Major Histocompatibility Complex - genetics; Membrane Proteins - physiology; Molecular Sequence Data; multidisciplinary; Mutation; Peptides; Precipitin Tests; Protein Biosynthesis; Proteins; PSF1 protein; Science; Science (multidisciplinary); Transformation, Genetic
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/355641a0

PRESENTATION of cytoplasmic antigens to class I-restricted cytotoxic T cells implied the existence of a specialized peptide transporter 1–3 (reviewed in ref. 4). For most class I heavy chains, association with peptides of the appropriate length is required for stable assembly with β 2 -microglobulin 5–11 . Mutant cells RMA–S (ref. 12) and .174/T2 (refs 13,14) 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 5–7 . The genetic defect in .174 has been localized to a large deletion in the class II region of the major histocompatibility complex 6,15,16 , within which two genes ( RING4 and RING11 ) have been identified that code for 'ABC' (ATP-binding cassette) transporters 15,17–21 . 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 (ref. 15), which lacks the RING4/PSF1 protein.