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Defective antigen processing correlates with a low level of intracellular glutathione
Author(s) -
Short Suzanna,
Merkel Brian J.,
Caffrey Rebecca,
McCoy Kathleen L.
Publication year - 1996
Publication title -
european journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.272
H-Index - 201
eISSN - 1521-4141
pISSN - 0014-2980
DOI - 10.1002/eji.1830261229
Subject(s) - glutathione , chinese hamster ovary cell , buthionine sulfoximine , biology , intracellular , cysteine , microbiology and biotechnology , antigen , biochemistry , transfection , glutathione disulfide , immunology , gene , enzyme , receptor
Abstract Previously, we reported that Chinese hamster ovary (CHO) cells transfected with murine mouse major histocompatibility complex class II genes, exhibit a unique antigen (Ag) processing defect whereby these cells are impaired in processing only Ag with disulfide bonds. Here, we examined various aspects of the intracellular reducing environment in the CHO cells to understand the underlying mechanism causing the defect. A cell hybrid generated by the fusion of CHO cells and L cell fibroblasts was used for comparison due to their competency in processing Ag. The transport pathway of cysteine within the CHO cells appeared normal. However, these cells had a significantly lower level of glutathione, a major physiological reducing thiol, compared to the cell hybrid. Treatment of the CHO cells with N‐acetyl‐ L ‐cysteine did not augment their glutathione content nor their ability to process Ag. When the cell hybrid was treated with L‐buthionine‐(S,R)‐sulfoximine (BSO), which significantly decreased their glutathione level, the hybrid poorly processed hen egg lysozyme (HEL) and ovalbumin, which have disulfide bonds. In contrast, BSO treatment did not affect the capacity of the hybrid to process pigeon cytochrome c and carboxymethylated HEL, which lack disulfide bonds. Therefore, low intracellular glutathione levels in antigen‐presenting cells correlated with defective processing of Ag with disulfide bonds, indicating that this thiol may be a critical factor in regulating productive Ag processing.