Alloreactive cytotoxic T cells provide means to decipher the immunopeptidome and reveal a plethora of tumor-associated self-epitopes.

摘要: HLA molecules presenting peptides derived from tumor-associated self-antigens (self-TAA) are attractive targets for T-cell-based immunotherapy of cancer. However, detection such epitopes is hampered by self-tolerance and limitations in the sensitivity mass spectrometry. Here, we used T cells HLA-A2-negative donors as tools to detect HLA-A2-bound two leukemia-associated differentiation antigens; CD20 previously undescribed cancer target myeloperoxidase. A high-throughput platform epitope discovery was designed using dendritic cotransfected with full-length transcripts self-TAA HLA-A2 allow presentation all naturally processed a predefined self-protein on foreign HLA. Antigen-reactive were directly detected panels color-coded peptide-HLA multimers containing predicted computer algorithm. Strikingly, cytotoxic generated against 37 out 50 bind HLA-A2. Among these, 36 undescribed. The allorestricted exquisitely peptide- HLA-specific responded strongly HLA-A2-positive leukemic endogenous expression or These results indicate that repertoire self-peptides presented class I has been underestimated wealth can be targeted when nontolerized T-cell repertoires.