Premium
Dendritic cells process synthetic long peptides better than whole protein, improving antigen presentation and T‐cell activation
Author(s) -
Rosalia Rodney A.,
Quakkelaar Esther D.,
Redeker Anke,
Khan Selina,
Camps Marcel,
Drijfhout Jan W.,
Silva Ana Luisa,
Jiskoot Wim,
Hall Thorbald,
Veelen Peter A.,
Janssen George,
Franken Kees,
Cruz Luis J.,
Tromp Angelino,
Oostendorp Jaap,
Burg Sjoerd H.,
Ossendorp Ferry,
Melief Cornelis J. M.
Publication year - 2013
Publication title -
european journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.272
H-Index - 201
eISSN - 1521-4141
pISSN - 0014-2980
DOI - 10.1002/eji.201343324
Subject(s) - antigen processing , antigen presentation , mhc class i , biology , internalization , transporter associated with antigen processing , mhc class ii , cross presentation , microbiology and biotechnology , antigen , dendritic cell , t cell , antigen presenting cell , proteasome , intracellular , immunology , major histocompatibility complex , immune system , cell , biochemistry
The efficiency of antigen ( A g) processing by dendritic cells ( DC s) is vital for the strength of the ensuing T ‐cell responses. Previously, we and others have shown that in comparison to protein vaccines, vaccination with synthetic long peptides ( SLP s) has shown more promising (pre‐)clinical results. Here, we studied the unknown mechanisms underlying the observed vaccine efficacy of SLP s. We report an in vitro processing analysis of SLP s for MHC class I and class II presentation by murine DC s and human monocyte‐derived DC s. Compared to protein, SLP s were rapidly and much more efficiently processed by DC s, resulting in an increased presentation to CD 4 + and CD 8 + T cells. The mechanism of access to MHC class I loading appeared to differ between the two forms of A g. Whereas whole soluble protein A g ended up largely in endolysosomes, SLP s were detected very rapidly outside the endolysosomes after internalization by DC s, followed by proteasome‐ and transporter associated with Ag processing‐dependent MHC class I presentation. Compared to the slower processing route taken by whole protein A gs, our results indicate that the efficient internalization of SLP s, accomplished by DC s but not by B or T cells and characterized by a different and faster intracellular routing, leads to enhanced CD 8 + T ‐cell activation.