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Making Peptides for Presentation A Pictorial Introduction SAMSI 3 March 2005.

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Presentation on theme: "Making Peptides for Presentation A Pictorial Introduction SAMSI 3 March 2005."— Presentation transcript:

1 Making Peptides for Presentation A Pictorial Introduction SAMSI 3 March 2005

2 Antigen Presentation Antigen – peptide (MHC Class I and MHC Class II) – lipids (CD1) – zwitterionic polysaccharides (MHC Class II) Peptide processing – endogenous (Class I) – exogenous (Class II) – cross-presentation (exogenous peptides via Class I)

3 MHC Class I Function – Presents cytoplasmic peptides to CD8 T cells – Viral & intracellular pathogens Machinery – Proteasome – Peptide loading complex – Peptidases cytosol ER Prefers 9-mers (closed ends)

4 MHC RibbonsMHC-peptide : T Cell Ribbons

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19 MHC Class II Function – Presents endocytosed peptides to CD4 cells – Extracellular pathogens – Antigen presenting cells only Machinery – Endosomes/lysosomes, extracellular(!) – Invariant chain – DM and DO – Endosomal proteases Invariant chain (Ii) processing Peptide cleavage Bind and trim Prefers … – eluted 13- to 22-mers (mode 17- to 19- mers) – can bind up to 51-mers with immunogenicity! – BUT core pockets fit a 9-mer, just like MHC Class I

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25 Determinant captureCompetitive capture

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29 Cross-Presentation Loading of exogenous ligands onto MHC Class I on APCs Essential for priming naïve CD8 T cells Vaccines targeting CD8 T cell responses Pathways: – particulate antigens – soluble antigens – direct inter-cellular transfer

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33 CD1 Function – Present lipids Group 1 – CD1a, CD1b, CD1c, CD1e – Recognised by conventional T cells – mainly microbial lipids Group 2 – CD1d – Recognised by Natural Killer T cells – mainly self lipids

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37 Speculations for vaccine design MHC Class I – DRiPs -> DNA vaccines which are designed to misfold (e.g. with kDel) – ERAP processing – proline in position 3 stops processing MHC Class II – multiple epitope vaccines –> spread out in space or time to minimize determinant capture conflicts – consider 3D structure -> pro-determinants CD1 – are lipids worth considering for vaccines?

38 References Immunology – Proteasome modeling – A mathematical model of protein degradation by the proteasome (2005, Biophys J preprint, Rob de Boer) – MAPPP: MHC class I antigenic peptide processing prediction (2003, Appl Bioinform, Mollenkopf) TAP modeling – Transporter associated with antigen processing preselection of peptides binding to the MHC: a bioinformatic evaluation (2004, J Immunol, Flower)


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