Intracellular transport of class I MHC molecules in antigen processing mutant cell lines

K. S. Anderson, J. Alexander, M. Wei, P. Cresswell

Research output: Contribution to journalArticle

101 Scopus citations

Abstract

Intracellular transport and stability of class I MHC glycoproteins depends on the assembly of H chain, β2-microglobulin and peptide. The Ag processing mutant cell lines T2 and RMA-S have defects in peptide loading of class I, resulting in reduced cell surface expression of class I molecules. Expression of class I molecules in the murine cell line RMA-S can be induced at 26°C, suggesting that they are transported to the cell surface, but are unstable. However, most human class I molecules in T2 are poorly expressed at the cell surface, even at 26°C. To directly compare the transport of human and mouse alleles in RMA-S and T2, the human alleles HLA-A2, A3, and B27 were transfected into RMA-S along with human β2-microglobulin, and the mouse alleles H-2Kb and Db were transfected into T2. Surface expression of HLA- A3 and B27 in RMA-S remained less than 10% of wild-type levels at 26°C. H- 2Kb and Db in both cell lines, however, were expressed at 20 to 30% wild- type levels at 37°C and could be induced to wild-type levels at 26°C or with peptides. The selective expression of murine class I glycoproteins at the cell surface of T2 is not because of their greater stability when associated with human β2m, since H-2Kb and Db H chain/human β2m complexes dissociate more rapidly in vitro than HLA-A3 and B27 complexes. These results suggest that the difference in transport between human and mouse class I in T2 reflects a fundamental structural property of the class I glycoproteins.

Original languageEnglish (US)
Pages (from-to)3407-3419
Number of pages13
JournalJournal of Immunology
Volume151
Issue number7
StatePublished - Jan 1 1993
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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