Ham-2 corrects the class I antigen-processing defect in RMA-S cells

• Published in: Nature (London) 1992-02, Vol.355 (6361), p.647-649
• Main Authors: Attaya, Michelle, Jameson, Stephen, Martinez, Coleen K, Hermel, Evan, Aldrich, Carla, Forman, James, Lindahl, Kirsten Fischer, Bevan, Michael J, Monaco, John J
• Format: Article
• Language: English
• Subjects: Animals; Antigens; ATP-Binding Cassette Sub-Family B Member 2; ATP-Binding Cassette Transporters; ATP-Binding Cassette, Sub-Family B, Member 3; Biochemistry; Biological and medical sciences; Carrier Proteins - physiology; Cell Line; Cellular biology; Cloning, Molecular; Cytotoxicity, Immunologic - genetics; Flow Cytometry; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Gene Expression Regulation; Genetics; Histocompatibility antigens (hla, h-2 and other systems); Histocompatibility Antigens Class I - biosynthesis; Histocompatibility Antigens Class II - physiology; Humanities and Social Sciences; Immunity (Disease); letter; Lymphocytes; Major Histocompatibility Complex - physiology; Mice; Molecular immunology; multidisciplinary; Science; Science (multidisciplinary); T-Lymphocytes, Cytotoxic - immunology; Transfection
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/355647a0

THE murine major histocompatibility complex (MHC) contains two genes ( Ham-1 and Ham-2 ) that encode members of a super-family of ATP-dependent transport proteins 1,2 . These genes are believed to mediate the transport of peptide antigen from the cytoplasm into the lumen of the endoplasmic reticulum for binding by MHC class I molecules. Evidence for such a function has come from the rescue of class I surface expression by a cloned copy of the human homologue of Ham-1 , PSF-1, in a human cell line that is defective in antigen processing 3 . A mutant murine cell line, RMA-S, has an identical antigen-processing-defective phenotype 4,5 . Here we show that expression of a cloned copy of the Ham-2 gene in RMA-S cells results in recovery of the ability to process and present class I-restricted antigens to cytotoxic T lymphocytes, and in partial recovery of class I surface expression. Processing defects for classical (H-2 K and D) and non-classical (Qal and HMT) class I molecules are corrected by Ham-2 . These data indicate that both MHC-linked transporter genes are probably required for class I antigen processing, and that the functional transporter in this pathway may consist of a Ham-l/Ham-2 heterodimer.