Assembly and cell surface expression of TAP-independent, chloroquine-sensitive and interferon-gamma-inducible class I MHC complexes in transformed fibroblast cell lines are regulated by tapasin.
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-gamma. The data imply that IFN-gamma 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.
Department of Cell Research and Immunology, The George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.
Sharon Vigodman
SV
Fromm
Shirly
S
Duady-Ben Yaakov
Chana
C
Schechter
Rachel
R
Ehrlich
D000256:Adenoviridae / Q000235:genetics / Q000378:metabolism; D000818:Animals; D017920:Antiporters / Q000235:genetics / Q000378:metabolism*; D002461:Cell Line, Transformed; D002469:Cell Separation; D002738:Chloroquine / Q000494:pharmacology*; D005347:Fibroblasts / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D005434:Flow Cytometry; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D007136:Immunoglobulins / Q000235:genetics / Q000378:metabolism*; D007371:Interferon-gamma / Q000494:pharmacology*; D046911:Macromolecular Substances; D008285:Major Histocompatibility Complex; D026901:Membrane Transport Proteins; D051379:Mice
D017920:Antiporters; D015395:Histocompatibility Antigens Class I; D007136:Immunoglobulins; D046911:Macromolecular Substances; D026901:Membrane Transport Proteins; C107762:tapasin; D007371:Interferon-gamma; D002738:Chloroquine