Prirodna antitela prisutna kod zdrave novorođenčadi koja prepoznaju peptid poreklom iz drugog konzerviranog regiona HIV-1 gp120
Sažetak
Uvod/Cilj. Visoka reaktivnost seruma na peptid NTM1, poreklom iz proteina omotača gp120 virusa humane imunodeficijencije, HIV-1, koreliše sa neprogresivnom HIV-1 infekcijom, a, takođe, može imati zaštitnu ulogu u kanceru dojke i prostate. Nedavno smo detektovali nizak titar antitela reaktivnih na NTM1 i u zdravim HIV-negativnim serumima i pokazali smo da se nivo ovih antitela može značajno povećati energičnom fizičkom aktivnošću. Međutim, postoje dokazi da je ovaj peptid neimunogen ili da je nevidljiv za imuni sistem čoveka, čime se sugeriše da NTM1 sekvenca obuhvata ili se preklapa sa određenim epitopom urođene imunosti. Cilj ove studije bio je da se dokumentuje da su vezivna antitela, NTMI, sastavni delovi urođenog humoralnog imunog odgovora potvđivanjem njihovog prisustva u serumu novorođenčadi. U tu svrhu, sakupili smo ukupno 225 urođenih sekvenci antigena prikazanih u literaturi i testirali ih za kandidate antigena sa najvećom sličnošću sekvence i spektra NTM1 nastalih iz HIV-1 gp120. Metode. Serumi 18 novorođenčadi testirani su ELISA probama sa NTM1 peptidom vezanim za ploču. Poravnavanje sekvenci urođenih antigena vršeno je bioinformatičkim alatom EMBOSS Water. Rezultati. U serumima HIV negativnih novorođenčadi identifikovali smo antitela reaktivna na NTM1. Dalje, da bi utvrdili koji od već poznatih antigena urođene imunosti je najsličniji peptidu NTM1, pretražili smo bazu sekvenci antigena urođene imunosti formirane na osnovu literaturih podataka. Ovo pretraživanje pokazalo je da, pored predhodno identifikovanog N-terminusa vazoaktivnog intestinalnog peptida, najsličnija je NTM1 peptidu sekvenca ribonukleoproteina RO60. Zaključak. Ovom studijom potvrdili smo hipotezu da su antitela koja prepoznaju NTM1 deo urođenog humoralnog imunog odgovora. Dalje, kompjuterskim pretraživanjem sličnosti utvrdili smo da su vazoaktivni intestinalni peptid i RO60 sekvence najsličnije NTM1 i, tako, najjači kandidati za antigene. U svetlu predstavljenih rezultata, privlačna je ideja da testiranje reaktivnosti krvi sa specifičnim urođenim antigenima, pre svega vazoaktivnim intestinalnim peptidom na rođenju, može otkriti potencijal za razvoj protektivnog imunog odgovora kasnije u životu i to ne samo za određene autoimune bolesti, već i za kancer dojke i prostate, kao i HIV infekcije.
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