P19-43. Regulatory T cell epitopes in a dendritic cell-targeted HIV vaccine delivery platform

Results Six highly promiscuous HLA class II T-cell epitopes in both the heavy and light chain constant domains of IgG were identified computationally. Epitopes were synthesized and shown to bind multiple HLA class II molecules with high affinity. These sequences specifically upregulate FoxP3 expression of CD4+CD25high T cells from healthy human donors. Co-incubation of these epitopes with various self and foreign antigens leads to antigen-specific suppression of effector T cell proliferation and cytokine secretion and an increase in IL-10 and CTLA-4 expression suggesting conversion of Teff to adaptive Tregs. The antiDEC-205 sequence was computationally screened for putative HLA DR4-restricted, regulatory T-cell epitopes using EpiMatrix. Epitopes were analyzed using OptiMatrix to select mutations that will reduce epitope binding affinity for HLA. Five regulatory T-cell epitopes were computationally identified. Per epitope, three modified sequences were selected and synthesized.