HAM-2 CORRECTS THE CLASS-I ANTIGEN-PROCESSING DEFECT IN RMA-S CELLS

被引:297
作者
ATTAYA, M
JAMESON, S
MARTINEZ, CK
HERMEL, E
ALDRICH, C
FORMAN, J
LINDAHL, KF
BEVAN, MJ
MONACO, JJ
机构
[1] VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,DEPT MICROBIOL & IMMUNOL,RICHMOND,VA 23298
[2] UNIV TEXAS,SW MED CTR,DEPT MICROBIOL,DALLAS,TX 75235
[3] UNIV WASHINGTON,HOWARD HUGHES MED INST,DEPT IMMUNOL,SEATTLE,WA 98195
[4] UNIV TEXAS,SW MED CTR,HOWARD HUGHES MED INST,DALLAS,TX 75235
[5] UNIV TEXAS,SW MED CTR,DEPT BIOCHEM,DALLAS,TX 75235
[6] UNIV TEXAS,SW MED CTR,GRAD IMMUNOL PROGRAM,DALLAS,TX 75235
关键词
D O I
10.1038/355647a0
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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 (Qa1 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-1/Ham-2 heterodimer.
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页码:647 / 649
页数:3
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