ABSTRACT
Tumor-specific neo-antigens that arise as a consequence of mutations are thought to be important for the therapeutic efficacy of cancer immunotherapies. Accumulating evidence suggests that neo-antigens may be commonly recognized by intratumoral CD8+ T cells, but it is unclear whether neo-antigen-specific CD4+ T cells also frequently reside within human tumors. In view of the accepted role of tumor-specific CD4+ T-cell responses in tumor control, we addressed whether neo-antigen-specific CD4+ T-cell reactivity is a common property in human melanoma.
Subject(s)
CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , Epitopes, T-Lymphocyte/immunology , Immunotherapy , Melanoma/immunology , Antigen Presentation/immunology , Antigens, Neoplasm/immunology , Cell Line, Tumor , DNA-Binding Proteins/genetics , Epitopes, T-Lymphocyte/genetics , Humans , Melanoma/genetics , Melanoma/pathology , Mutation , Proto-Oncogene Proteins c-bcl-6 , bcl-X Protein/geneticsABSTRACT
Post-translational modification of proteins with ubiquitin (Ub) and Ub chains controls numerous biochemical events. Although it has been proven that all Ub-Ub linkages are formed in cells, studies have been limited for a long time to K48 and K63 chains as these can be generated biochemically. Access to the remaining (atypical) Ub-Ub chain types has been hampered by a lack of specific E2 enzymes. In this chapter we present a solution to this problem by using a native chemical ligation approach to obtain all other (i.e. K6, K11, K27, K29 and K33) diubiquitin chains.
