Prolonged antigen presentation is required for optimal CD8+ T cell responses against malaria liver stage parasites.

Immunization with irradiated sporozoites is currently the most effective vaccination strategy against liver stages of malaria parasites, yet the mechanisms underpinning the success of this approach are unknown. Here we show that the complete development of protective CD8+ T cell responses requires p...

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Autores principales:	Ian A Cockburn, Yun-Chi Chen, Michael G Overstreet, Jason R Lees, Nico van Rooijen, Donna L Farber, Fidel Zavala
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/1529fb508d934fd49006eb89a8e82342
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spelling	oai:doaj.org-article:1529fb508d934fd49006eb89a8e823422021-12-02T20:00:42ZProlonged antigen presentation is required for optimal CD8+ T cell responses against malaria liver stage parasites.1553-73661553-737410.1371/journal.ppat.1000877https://doaj.org/article/1529fb508d934fd49006eb89a8e823422010-05-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20463809/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Immunization with irradiated sporozoites is currently the most effective vaccination strategy against liver stages of malaria parasites, yet the mechanisms underpinning the success of this approach are unknown. Here we show that the complete development of protective CD8+ T cell responses requires prolonged antigen presentation. Using TCR transgenic cells specific for the malaria circumsporozoite protein, a leading vaccine candidate, we found that sporozoite antigen persists for over 8 weeks after immunization--a remarkable finding since irradiated sporozoites are incapable of replication and do not differentiate beyond early liver stages. Persisting antigen was detected in lymphoid organs and depends on the presence of CD11c+ cells. Prolonged antigen presentation enhanced the magnitude of the CD8+ T cell response in a number of ways. Firstly, reducing the time primed CD8+ T cells were exposed to antigen in vivo severely reduced the final size of the developing memory population. Secondly, fully developed memory cells expanded in previously immunized mice but not when transferred to naïve animals. Finally, persisting antigen was able to prime naïve cells, including recent thymic emigrants, to become functional effector cells capable of eliminating parasites in the liver. Together these data show that the optimal development of protective CD8+ T cell immunity against malaria liver stages is dependent upon the prolonged presentation of sporozoite-derived antigen.Ian A CockburnYun-Chi ChenMichael G OverstreetJason R LeesNico van RooijenDonna L FarberFidel ZavalaPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 6, Iss 5, p e1000877 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Ian A Cockburn Yun-Chi Chen Michael G Overstreet Jason R Lees Nico van Rooijen Donna L Farber Fidel Zavala Prolonged antigen presentation is required for optimal CD8+ T cell responses against malaria liver stage parasites.
description	Immunization with irradiated sporozoites is currently the most effective vaccination strategy against liver stages of malaria parasites, yet the mechanisms underpinning the success of this approach are unknown. Here we show that the complete development of protective CD8+ T cell responses requires prolonged antigen presentation. Using TCR transgenic cells specific for the malaria circumsporozoite protein, a leading vaccine candidate, we found that sporozoite antigen persists for over 8 weeks after immunization--a remarkable finding since irradiated sporozoites are incapable of replication and do not differentiate beyond early liver stages. Persisting antigen was detected in lymphoid organs and depends on the presence of CD11c+ cells. Prolonged antigen presentation enhanced the magnitude of the CD8+ T cell response in a number of ways. Firstly, reducing the time primed CD8+ T cells were exposed to antigen in vivo severely reduced the final size of the developing memory population. Secondly, fully developed memory cells expanded in previously immunized mice but not when transferred to naïve animals. Finally, persisting antigen was able to prime naïve cells, including recent thymic emigrants, to become functional effector cells capable of eliminating parasites in the liver. Together these data show that the optimal development of protective CD8+ T cell immunity against malaria liver stages is dependent upon the prolonged presentation of sporozoite-derived antigen.
format	article
author	Ian A Cockburn Yun-Chi Chen Michael G Overstreet Jason R Lees Nico van Rooijen Donna L Farber Fidel Zavala
author_facet	Ian A Cockburn Yun-Chi Chen Michael G Overstreet Jason R Lees Nico van Rooijen Donna L Farber Fidel Zavala
author_sort	Ian A Cockburn
title	Prolonged antigen presentation is required for optimal CD8+ T cell responses against malaria liver stage parasites.
title_short	Prolonged antigen presentation is required for optimal CD8+ T cell responses against malaria liver stage parasites.
title_full	Prolonged antigen presentation is required for optimal CD8+ T cell responses against malaria liver stage parasites.
title_fullStr	Prolonged antigen presentation is required for optimal CD8+ T cell responses against malaria liver stage parasites.
title_full_unstemmed	Prolonged antigen presentation is required for optimal CD8+ T cell responses against malaria liver stage parasites.
title_sort	prolonged antigen presentation is required for optimal cd8+ t cell responses against malaria liver stage parasites.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/1529fb508d934fd49006eb89a8e82342
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Prolonged antigen presentation is required for optimal CD8+ T cell responses against malaria liver stage parasites.

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