Genetic fusion of proteins to the SIV Tat protein enhances their immunogenicity

Peptide immunization against the C-terminal of alpha-synuclein reduces locomotor activity in mice overexpressing alpha-synuclein

“…These two signals can be activated by the Ct-αSyn complex. For example, the Ct-αSyn complex contains an arginine-rich motif, which allows its binding to cell surfaces to present multiple copies of αSyn 110–130 to B cells to induce surface Ig crosslink [ 33 ]. The helper T cell response induced by the PADRE epitope is strong enough to activate αSyn 110–130 -specific B cells without the requirement of clustering surface Ig receptors by multivalent αSyn 110–130 [ 32 ].…”

“…A linear peptide (Ct-αSyn complex; Fig 1 ) composed of a pan-DR T helper epitope (PADRE: AKFVAAWTLKAAA), an arginine-rich motif (GGRKRRRTPKKAKGG) derived from the simian immunodeficiency virus (SIV) Tat protein, and an αSyn C-terminal region (αSyn 110–130 : EGILEDMPVDPDNEAYEMPSE) was synthesized with purity greater than 80% by Genomics Ltd. This synthetic peptide was adsorbed onto alum salts to immunize mice, as described in our previous work [ 33 ]. Briefly, 5 ml of PBS, 500 μl of 1M NaHCO 3 , and 1 ml of 10% alum [AlK(SO 4 ) 2 ] were thoroughly mixed to form a milky solution.…”

“…PADRE is a non-natural peptide binding with high or intermediate affinity to several common HLA-DR and mouse MHC class II alleles, capable of stimulating helper T cells to induce antibody responses to the linked peptide [ 31 , 32 ]. In addition, the arginine-rich motif, derived from the simian immunodeficiency virus (SIV) Tat protein, is able to amplify antibody responses to its fusion protein, although the mechanism of action is unknown [ 33 ].…”