Efficiency and mechanism of antigen-specific CD8+ T-cell activation using synthetic long peptides.
Synthetic long peptides that contain immunogenic T-cell epitopes have been used to induce activation of antigen-specific CD8 T cells in vitro for immune monitoring or adoptive transfer, or in vivo after peptide vaccination. However, the efficiency and mechanisms of presentation of exogenous long peptides in human leukocyte antigen (HLA) class I remain to be elucidated. In this study, we demonstrated that the efficiency of antigen-specific CD8 T-cell activation using extended peptide variants of common viral epitopes is variable. We demonstrated that processing and HLA class I presentation of the long peptides were not dependent on the proteasome and transporter associated with antigen processing, illustrating that the classic route of HLA class I presentation was not required for activation of specific CD8 T cells by exogenous synthetic long peptides. Although long peptides were shown to bind to the relevant HLA class I molecules, peptide trimming was likely to be essential for optimal HLA class I presentation and T-cell activation. As the proteasome was not required for processing of exogenous peptides, it is very likely that peptide trimming was mediated by peptidases, which may be located extracellularly at the cell surface, in the cytosol, endoplasmic reticulum, or in endosomal and lysosomal compartments. Furthermore, the results suggested that processing of the correct minimal peptides was facilitated by binding in HLA class I molecules. This mechanism of HLA-guided processing may be important in HLA class I presentation of exogenous long peptides to induce activation of specific CD8 T cells.
Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden, The Netherlands. m.l.zandvliet@lumc.nl
Maarten L
ML
Zandvliet
Michel G D
MG
Kester
Ellis
E
van Liempt
Arnoud H
AH
de Ru
Peter A
PA
van Veelen
Marieke
M
Griffioen
Henk-Jan
HJ
Guchelaar
J H Frederik
JH
Falkenburg
Pauline
P
Meij
D000595:Amino Acid Sequence; D017951:Antigen Presentation / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002851:Chromatography, High Pressure Liquid; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology*; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000276:immunology*
D018984:Epitopes, T-Lymphocyte; D015395:Histocompatibility Antigens Class I; D010455:Peptides