ASSEMBLY AND FUNCTION OF THE 2 ABC TRANSPORTER PROTEINS ENCODED IN THE HUMAN MAJOR HISTOCOMPATIBILITY COMPLEX

Article

关键词: TOXIC LYMPHOCYTES-T;    CLASS-II REGION;    HLA-B ANTIGENS;    MONOCLONAL-ANTIBODY;    INFLUENZA NUCLEOPROTEIN;    MULTIDRUG RESISTANCE;    MOLECULAR ANALYSIS;    CYSTIC-FIBROSIS;    HEAVY-CHAINS;    MHC;   

DOI  :  10.1038/355641a0

来源: SCIE

【 摘 要 】

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 beta-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.

【 授权许可】

Free