Divergent paths for the selection of immunodominant epitopes from distinct antigenic sources.
Nat Commun
; 5: 5369, 2014 Nov 21.
Article
em En
| MEDLINE
| ID: mdl-25413013
ABSTRACT
Immunodominant epitopes are few selected epitopes from complex antigens that initiate T-cell responses. Here to provide further insights into this process, we use a reductionist cell-free antigen-processing system composed of defined components. We use the system to characterize steps in antigen processing of pathogen-derived proteins or autoantigens and we find distinct paths for peptide processing and selection. Autoantigen-derived immunodominant epitopes are resistant to digestion by cathepsins, whereas pathogen-derived epitopes are sensitive. Sensitivity to cathepsins enforces capture of pathogen-derived epitopes by major histocompatibility complex class II (MHC class II) before processing, and resistance to HLA-DM-mediated-dissociation preserves the longevity of those epitopes. We show that immunodominance is established by higher relative abundance of the selected epitopes, which survive cathepsin digestion either by binding to MHC class II and resisting DM-mediated-dissociation, or being chemically resistant to cathepsins degradation. Non-dominant epitopes are sensitive to both DM and cathepsins and are destroyed.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Autoantígenos
/
Proteínas Virais
/
Linfócitos T
/
Epitopos Imunodominantes
/
Virus da Influenza A Subtipo H5N1
Limite:
Humans
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article