Reconstitution of expression of H-2K region-encoded murine MHC class I glycoproteins in MHC class I-deficient B16BL6 melanoma cells affects the expression and function of antigen-processing machinery.
We have recently reported that reconstitution of expression of major histocompatibility complex (MHC) class I glycoproteins in MHC-deficient and highly metastatic B16BL6 melanoma cells attenuates their malignant capacities by modulation of compartmentalization and functions of cell membrane receptors for growth factors [Assa-Kunik E, et al. J Immunol 2003;171:2945-52]. Our present study provides evidence that re-expression of an H-2K MHC class I-encoding gene in these cells also augments the expression of the Tap-2 peptide transporter and the inducible proteasome subunits, i.e. Lmp-2, Lmp-7 and Lmp-10. Up-regulation of inducible proteasome subunits was also followed by a significant changed in the proteolytic activity of the proteasome complex. We suggest that, in addition to providing a framework for proper presentation of antigenic peptides, MHC class I glycoproteins may regulate the immune response by modulating the expression and function of other genes, whose products are essential for proper antigen processing and presentation.
Tsory
Sylvia
S
Department of Immunology and Microbiology, Ben-Gurion University Cancer Research Center, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel.
Kellman-Pressman
Sigal
S
Fishman
Daniel
D
Segal
Shraga
S
D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D000818:Animals; D017951:Antigen Presentation; D045744:Cell Line, Tumor; D002999:Clone Cells; D005805:Genes, MHC Class I; D006183:H-2 Antigens / Q000235:genetics*; D008546:Melanoma, Experimental / Q000235:genetics*; D051379:Mice; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D015854:Up-Regulation
D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters; D006183:H-2 Antigens; C489516:Tap2 protein, mouse; D046988:Proteasome Endopeptidase Complex