Abstracts (complete list) - Wissenschaft Online

Wolfram Osen, Mingxia Song, Sabine Soltek, Barbara Leuchs, Julia Steitz, Xuan Duc
Ngyuen, Dirk Schadendorf, Annette Paschen
Identification of novel CD4+ T cell epitopes from human
tyrosinase related protein 2 (TRP-2) by a combinatorial
approach based on the immunisation of HLA-transgenic mice
with recombinant Adenovirus and antigen peptide library
screening
Melanoma differentiation antigen TRP-2 is a target of spontaneous cytotoxic CD8+ T cell
(CTL) responses in tumor patients and can thus be considered as a melanoma
associated tumor antigen (TA). Since induction and maintenance of tumor-specific CD8
+ T cell responses depends on the activity of specific CD4+ T helper (Th) cells, we set
out to identify novel TRP-2-specific Th epitopes that could be included in
immunotherapy approaches against malignant melanoma. Using recombinant
Adenovirus expressing human TRP-2 (Ad/TRP-2) as an immunogen followed by
combinatorial peptide library screening in vitro we were able to identify novel
DRB1*0301-restricted T cell epitopes in HLA-DRB1*0301 transgenic mice. Notably, the
same epitope was found to be recognized by Th cells of DRB1*03+ donors on syngeneic
Ad/TRP-2 infected DC, showing that the epitope identified in the HLA-DRB1*0301
transgenic mouse system is also processed and presented by human DRB1*03+
individuals.