Regulation of MHC class I membrane expression by beta 2-microglobulin.

Abstract

MHC-I binding peptides and beta 2 microglobulin (beta 2-m) can upregulate the MHC-I heavy chain expression on certain peptide transporter mutant cells. We have further studied this with normal cells and non-mutant cell lines. No MHC-I upregulation was seen with normal, resting or activated T cells. On mouse cell lines P815 and B16, both peptides and human beta 2-m gave an additive upregulation response. With the human small cell lung carcinoma H82, an optimal HLA.A2 binding peptide (GILGFVFTL) gave an upregulation response, whereas beta 2-m alone or in combination with this peptide had no effect. However, beta 2-m potentiated the response of H82 cells to a slightly longer peptide. Using mutant RMA-S cells, it was found that both Brefeldin A (BFA) and chloroquine, but not leupeptin, inhibited MHC-I upregulation response to both peptide and beta 2-m. In contrast to chloroquine, BFA also gave a reduction of background membrane MHC-I expression, presumably due to a block in Golgi transport. Human beta 2-m, which binds to RMA-S cells, and which is known to internalize into endosomes, did not reappear on the cell surface. When Db on RMA-S cells was upregulated by human beta 2-m, the sensitivity of these cells to Db restricted CTL cells increased. Even if beta 2-m did not upregulate the overall MHC-I expression on normal cells, it may still quantitatively increase the expression of optimally presented peptides and endosomal recycling many be important in this process.

• Authors: U M Abdel Motal, M X Zhou, A R Siddiqi, M Jondal
• Journal: Scandinavian journal of immunology (Scand J Immunol) Vol. 38 Issue 4 Pg. 395-400 (Oct 1993) ISSN: 0300-9475 [Print] England
• PMID: 8211001 (Publication Type: Journal Article)

Chemical References

• Anti-Bacterial Agents
• Antigens, Surface
• Cyclopentanes
• Histocompatibility Antigens Class I
• Peptides
• beta 2-Microglobulin
• Brefeldin A
• Chloroquine

Topics

• Amino Acid Sequence
• Animals
• Anti-Bacterial Agents (pharmacology)
• Antigens, Surface (immunology)
• Brefeldin A
• Chloroquine (pharmacology)
• Cyclopentanes (pharmacology)
• Flow Cytometry
• Histocompatibility Antigens Class I (immunology)
• Humans
• Mice
• Molecular Sequence Data
• Peptides (immunology)
• T-Lymphocytes, Cytotoxic (immunology)
• Tumor Cells, Cultured
• Up-Regulation (drug effects)
• beta 2-Microglobulin (immunology)