Amine‐reactive OVA multimers for auto‐vaccination against cytokines and other mediators: perspectives illustrated for GCP‐2 in L. major infection

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

关键词: vaccine;    interleukin;    chemokine;    cross‐;    linking;    antigen;   

DOI  :  10.1189/jlb.1210699

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Anticytokineauto‐vaccinationisapowerfultoolforthestudyofcytokinefunctionsinvivobuthasremainedratheresotericasaresultofnumeroustechnicaldifficulties.Weheredescribeatwo‐stepprocedurebasedontheuseofOVAmultimerspurifiedbysizeexclusionchromatographyafterincubationwithglutaraldehydeatpH6.WhensuchpolymersareincubatedwithatargetproteinatpH8.5todeprotonatereactiveamines,complexesareformedthatconferimmunogenicitytoself‐antigens.ThechemokineGCP‐2/CXCL6,thecytokinesGM‐CSF,IL‐17F,IL‐17E/IL‐25,IL‐27,andTGF‐β1,andtheMMP‐9/gelatinaseBarediscussedasexamples.mAb,derivedfromsuchimmunizedmice,haveobviousadvantagesforinvivostudiesofthetargetproteins.UsingamAbagainstGCP‐2,obtainedbythemethoddescribedhere,weprovidethefirstdemonstrationofthemajorroleplayedbythischemokineinrapidneutrophilmobilizationafterLeishmaniamajorinfection.Pre‐activatedOVAmultimersreactivewithamineresiduesthusprovideanefficientcarrierforauto‐vaccinationagainst9–90kDaautologousproteins...

【 授权许可】

CC BY