Ham-2 corrects the class I antigen-processing defect in RMA-S cells
- 1 February 1992
- journal article
- letter
- Published by Springer Nature in Nature
- Vol. 355 (6361) , 647-649
- https://doi.org/10.1038/355647a0
Abstract
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 proteins1,2. 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 processing3. A mutant murine cell line, RMA-S, has an identical antigen-processing-defective phenotype4,5. 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.Keywords
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