Enkel-keten antilichamen tegen actinebindende eiwitten als tool voor het bestuderen van de immuunrespons in dendritische cellen

Nincy Debeuf
Persbericht

Enkel-keten antilichamen tegen actinebindende eiwitten als tool voor het bestuderen van de immuunrespons in dendritische cellen

Voetjes van immuuncellen verdwijnen met alpaca antilichamen

Iedereen lijdt wel eens aan een verstoring van het immuunsysteem. Een te zwak reagerend immuunsysteem maakt ons gevoelig voor infecties. Een te sterk reagerend immuunsysteem kan leiden tot auto-immuunziekten of allergieën. Het is dus belangrijk dat ons immuunsysteem in balans is en daar zorgen onze dendritische cellen voor.  

Dendritische cellenDendritische cellen zijn belangrijke verdedigingscellen die binnentredende micro-organismen vangen en vervolgens de andere immuuncellen verwittigen om een immuunreactie te starten. Dendritische cellen moeten voor hun boodschappersfunctie een grote afstand afleggen en zijn dan ook zeer beweeglijk. Ze maken daarbij gebruik van podosomen, te vergelijken met de voetjes van de cel.  Een podosoom (lees: voetje) is opgebouwd uit meerdere eiwitten, waaronder fascine en cortactine. Deze eiwitten bestaan uit meerdere domeinen (lees: fragmenten) en welk domein nu precies belangrijk is in de podosomen was tot voor kort onduidelijk.

Alpaca antilichamen en nanobodiesOm de precieze rol van fascine en cortactine in de ‘voetjes’  te onderzoeken, werd gebruik gemaakt van nanobodies. Nanobodies zijn kleine eiwitten die voorkomen in het bloed van kameelachtigen, zoals alpaca’s. Doordat deze nanobodies zo klein en stabiel zijn, kunnen ze worden gebruikt om één welbepaald domein van een eiwit (zoals fascine en cortactine) uit te schakelen. De andere domeinen van het eiwit worden gespaard. Dit is een groot voordeel tegenover andere onderzoekstechnieken die het volledige eiwit uitschakelen.

Voetjes verdwijnenIsabel Van Audenhove (Doctoraatsstudente UGent) en Nincy Debeuf (masterstudente UGent) brachten nanobodies in dendritische cellen om één domein van fascine en cortactine uit te schakelen. Er werd gewerkt met menselijke dendritische cellen die geïsoleerd werden uit het bloed van gezonde vrijwilligers. De nanobodies werden via een elektrische puls binnenin de cellen gebracht en vervolgens werden de cellen microscopisch bestudeerd. Zo werd gezien dat het inbrengen van de nanobodies tegen een fascine en cortactine domein leidde tot het verdwijnen van de ‘voetjes’ van dendritische cellen. Bovendien zagen de dendritische cellen er veel minder beweeglijk uit. In het lichaam zou dit betekenen dat de boodschappersfunctie van deze immuuncellen is aangetast.  

Toekomst met nanobodiesNaast het aantonen dat welbepaalde domeinen van fascine en cortactine nodig zijn voor de voetjes van dendritische cellen, is deze masterproef ook een mooi voorbeeld van de toepassingsmogelijkheden van nanobodies. Vaak worden nanobodies gebruikt om eiwitten buiten de cel te beïnvloeden. Hier werd aangetoond dat nanobodies ook binnenin de cel geraken en effecten hebben, zelfs op eiwitten die niet door de klassieke geneesmiddelen bereikt kunnen worden. De onderzoeksgroep van professor Gettemans (UGent), tevens promoter van deze masterproef, heeft ook al kunnen aantonen dat kankereiwitten geblokkeerd kunnen worden met nanobodies. Zo zorgden nanobodies in muizen voor minder uitzaaiingen van borstkankercellen. Er wordt dan ook verwacht dat nanobodies in de toekomst een nieuwe klasse van medicijnen zullen vormen.

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Universiteit of Hogeschool
Biomedische Wetenschappen
Publicatiejaar
2014
Kernwoorden
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