Ionizing Radiation Affects Human MART-1 Melanoma Antigen Processing and Presentation by Dendritic Cells

摘要: Radiation is generally considered to be an immunosuppressive agent that acts by killing radiosensitive lymphocytes. In this study, we demonstrate the noncytotoxic effects of ionizing radiation on MHC class I Ag presentation bone marrow-derived dendritic cells (DCs) have divergent consequences depending upon whether peptides are endogenously processed and loaded onto molecules or added exogenously. The endogenous pathway was examined using C57BL/6 murine DCs transduced with adenovirus express human melanoma/melanocyte recognized T (AdVMART1). Prior irradiation abrogated ability AdVMART1-transduced induce MART-1-specific cell responses following their injection into mice. these same generate protective immunity against B16 melanoma, which expresses MART-1, also radiation. Failure antitumor not due cytotoxicity radiation-induced block in DC maturation loss expression costimulatory molecules. Expression some affected, but because actually enhanced lymphocyte peptide MART-1(27-35) immunodominant context HLA-A2.1, they were unlikely critical. increase reactivity generated irradiated pulsed protected mice growth B16-A2/K(b) tumors HLA-A2.1/K(b) transgenic Taken together, results suggest modulates I-mediated functionally affecting pathways.