Assembly and cell surface expression of TAP-independent, chloroquine-sensitive and interferon-γ-inducible class I MHC complexes in transformed fibroblast cell lines are regulated by tapasin

Sharon Vigodman Fromm, Shirly Duady-Ben Yaakov, Chana Schechter, Rachel Ehrlich*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Antigen processing and presentation by class I MHC molecules generally require assembly with peptide epitopes generated by the proteasome and transported into the ER by the transporters associated with antigen presentation (TAP). Recently, TAP-independent pathways supporting class I MHC-mediated presentation of exogenous antigens, as well as of endogenously synthesized viral antigens, were described. We now characterize a TAP-independent pathway that is operative in both TAP1- and TAP2-deficient Adenovirus (Ad)-transformed fibroblast cell lines. To the best of our knowledge, this is the first time that the existence of such a pathway has been described in non-infected cells that do not belong to the hematopoietic lineage. We show that this pathway is proteasome-independent and chloroquine-sensitive. Cell surface expression of these TAP-independent class I complexes is modulated by tapasin levels and is enhanced by IFN-γ. The data imply that IFN-γ increases the relative level of TAP-independent high affinity class I complexes that exit the ER on their way to the cell surface and to vacuolar compartments where peptide cleavage/exchange might take place before recycling to the cell surface. Since both TAP and tapasin expression are altered in numerous tumors and in virus-infected cells, TAP-independent class I complexes may be a valuable target source for immune responses.

Original languageEnglish
Pages (from-to)207-218
Number of pages12
JournalCellular Immunology
Volume215
Issue number2
DOIs
StatePublished - 2002

Funding

FundersFunder number
Association for International Cancer Research
German-Israeli Foundation for Scientific Research and Development
Israel Science Foundation
Association for International Cancer Research

    Keywords

    • Antigen processing
    • Cell trafficking
    • Cytokines
    • MHC
    • Peptides

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