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

Journal article

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.

Authors: Kelly, A; Powis, S; Kerr, L; Mockridge, I; Elliott, T

• Publication status: Published
• Journal: Nature
• Volume: 355
• Issue: 6361
• Pages: 641-644
• Publication date: 1992-02-01
• DOI: 10.1038/355641a0
• EISSN: 1476-4687
• ISSN: 0028-0836
• Language: English
• Keywords: Humans; ATP-Binding Cassette Transporters; Carrier Proteins; Genotype; Amino Acid Sequence; Precipitin Tests; Histocompatibility Antigens Class I; Molecular Sequence Data; Electrophoresis, Polyacrylamide Gel; Gene Expression; Base Sequence; Major Histocompatibility Complex; Mutation; Transformation, Genetic; Membrane Proteins; Blotting, Southern; Protein Biosynthesis