Targeted delivery of peptide epitopes to class I major histocompatibility molecules by a modified Pseudomonas exotoxin.

AUTOR(ES)

Donnelly, J J

RESUMO

Cytotoxic T lymphocytes (CTLs) expressing the CD8 surface marker recognize peptides in association with major histocompatibility complex (MHC) class I molecules. Although most peptides expressed on MHC class I molecules are derived from self- or virally encoded proteins, delivery of exogenous proteins to the cytosol can result in their being processed for presentation to CTLs on MHC class I molecules. We describe two fusion proteins (PEMa and PENP), consisting of the binding and translocating domains of Pseudomonas exotoxin A (PE), fused to peptide epitopes from influenza A matrix protein and nucleoprotein, respectively. These fusion proteins were internalized and processed by MHC class I-positive target cells, resulting in sensitization of target cells for lysis by peptide-specific CTLs. A point mutation known to interfere with intoxication by wild-type PE also reduced the ability of PEMa to sensitize target cells. Fusion of peptide or polypeptide epitopes with PE provides a potential means of eliciting CTLs without the use of self-replicating agents, as well as a useful probe for studying MHC class I-restricted antigen processing.

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