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 th e evaluation of T cell-based immunization and vaccination strategies, altho ugh deficient MHC class I surface expression has been identified in these c ells, We postulate here that the MHC class I-deficient phenotype of B16 mel anoma cells is attributable to down-regulation or the loss of the expressio n and function of multiple components of the MHC class I antigen-processing pathway, including the peptide transporter associated with antigen process ing, the proteasome subunits LMP2, LMP7, and LMP10, PA28 alpha and -beta, a nd the chaperone tapasin, In contrast, calnexin, calreticulin, ER60, and pr otein disulfide isomerase expression are unaltered or only marginally suppr essed in these cells. The level of down-regulation of the components of the antigen-processing pathway is either transcriptionally or posttranscriptio nally controlled and could be corrected in all cases by IFN-gamma treatment , which also reconstituted MHC class I surface expression. Thus, B16 melano ma cells can be used as a model for the characterization of the mechanisms underlying the coordinated dysregulation of the antigen-processing componen ts, which should provide new insights into the development of tumors and th e factors controlling this process.