Characterization of the major histocompatibility complex class I deficiencies in B16 melanoma cells.
The murine B16 melanoma system represents an important in vivo model for the evaluation of T cell-based immunization and vaccination strategies, although deficient MHC class I surface expression has been identified in these cells. We postulate here that the MHC class I-deficient phenotype of B16 melanoma cells is attributable to down-regulation or the loss of the expression and function of multiple components of the MHC class I antigen-processing pathway, including the peptide transporter associated with antigen processing, the proteasome subunits LMP2, LMP7, and LMP10, PA28alpha and -beta, and the chaperone tapasin. In contrast, calnexin, calreticulin, ER60, and protein disulfide isomerase expression are unaltered or only marginally suppressed in these cells. The level of down-regulation of the components of the antigen-processing pathway is either transcriptionally or posttranscriptionally controlled and could be corrected in all cases by IFN-y treatment, which also reconstituted MHC class I surface expression. Thus, B16 melanoma cells can be used as a model for the characterization of the mechanisms underlying the coordinated dysregulation of the antigen-processing components, which should provide new insights into the development of tumors and the factors controlling this process.
Seliger
B
B
Johannes Gutenberg Universität, III. Medizinische Klinik, Mainz, Germany. B.Seliger@3-med.klinik.uni-mainz.de
Wollscheid
U
U
Momburg
F
F
Blankenstein
T
T
Huber
C
C
D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis / Q000235:genetics; D026905:Amino Acid Transport Systems; D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects / Q000235:genetics* / Q000276:immunology; D004195:Disease Models, Animal; D015536:Down-Regulation; D005095:Exoribonucleases / Q000096:biosynthesis / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006183:H-2 Antigens / Q000096:biosynthesis / Q000276:immunology*; D007371:Interferon-gamma / Q000494:pharmacology; D008546:Melanoma, Experimental / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D011994:Recombinant Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D029701:Saccharomyces cerevisiae Proteins; D014407:Tumor Cells, Cultured
D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters; D026905:Amino Acid Transport Systems; D006183:H-2 Antigens; D011994:Recombinant Proteins; D029701:Saccharomyces cerevisiae Proteins; C429825:TAT2 protein, S cerevisiae; C489516:Tap2 protein, mouse; D007371:Interferon-gamma; D005095:Exoribonucleases