I-Domain-Antigen Conjugate (IDAC) for Delivering Antigenic Peptides to APC: Synthesis, Characterization, and in Vivo EAE Suppression
I-Domain-Antigen Conjugate (IDAC) for Delivering Antigenic Peptides to APC: Synthesis, Characterization, and in Vivo EAE Suppression
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DOI：
10.1021/bc200580j
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发表时间：
2012-03-01
影响因子：
4.7
通讯作者：
Siahaan, Teruna J.
中科院分区：
文献类型：
--
作者：
Manikwar, Prakash;Bueyuektimkin, Barlas;Siahaan, Teruna J.
The objectives of this work are to characterize the identity of I-domain-antigen conjugate (IDAC) and to evaluate the in vivo efficacy of IDAC in suppressing experimental autoimmune encephalomyelitis (EAE) in mouse model. The hypothesis is that the I-domain delivers PLP139-151 peptides to antigen-presenting cells (APC) and alters the immune system by simultaneously binding to ICAM-1 and MHC-II, blocking immunological synapse formation. IDAC was synthesized by derivatizing the lysine residues with maleimide groups followed by conjugation with PLP-Cys-OH peptide. Conjugation with PLP peptide does not alter the secondary structure of the protein as determined by CD. IDAC suppresses the progression of EAE, while I-domain and GMB-I-domain could only delay the onset of EAE. As a positive control, Ac-PLP-BPI-NH2-2 can effectively suppress the progress of EAE. The number of conjugation sites and the sites of conjugations in IDAC were determined using tryptic digest followed by LC-MS analysis. In conclusion, conjugation of I-domain with an antigenic peptide (PLP) resulted in an active molecule to suppress EAE in vivo.
