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Reju
This document summarizes antigen processing and presentation. It discusses how antigens are processed by antigen presenting cells (APCs) like dendritic cells, macrophages, and B cells. Native proteins are broken down into peptides via the proteasome and transported into the endoplasmic reticulum by TAP transporters. There, they bind to MHC class I or II molecules and are presented on the APC surface to CD8+ or CD4+ T cells, respectively. Professional APCs like dendritic cells are most effective at stimulating naive T cells.
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Reju
- 1. ANTIGEN PROCESSING ANDPRESENTATIONV.Reju
- 2. ANTIGEN PROCESSINGThe conversionof native proteins to peptides which can combine with MHC molecules
- 3. ANTIGEN PRESENTATIONThe courseof formation and display of peptide-MHC complexes on the surface of APCs and the course of peptide MHC complexes recognition by T cells
- 4. ANTIGEN PRESENTING CELLS A group of cells that play important role in immune response which can uptake ,process antigens and present peptide-MHC complexes to T cells
- 5. GENERAL PROPERTIES OFAPCCapacity to uptake proteinsAbility to process proteins to peptidesCapacity to present peptides depends on type of MHC molecules expressedMust express co-stimulatory signals for T cell stimulation
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- 8. B cellNON-PROFESSIONAL APCs Fibroblast
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- 10. Thyroid epithelialcells
- 11. Pancreatic betacells
- 12. vascular endothelialcellsDENDRITIC CELLSFirst found by Steinman in 1973Cultured in vitro in 1993 by InabaGenerated from bone marrow in presence of cytokine granulocyte-macrophage colony stimulating factorCan stimulate naive T cell
- 13. WHY DENDRITIC CELLSARE CONSIDERED AS MOST EFFECTIVE APC??????
- 14. MACROPHAGE (MΦ)First identified APCDifferentiated from monocyte in bloodCannot stimulate naïve T cellCapture antigens by phagocytosis ,pinocytosis and receptor mediated phagocytosis
- 15. B CELLSOriginates inbone marrow Mature B cell co-express IgM and IgD on their cell surface
- 16. SELF MHC RESTRICTIONOF T CELLCD 4+ and CD 8+ cells recognize antigen only in presence of MHC MHC I + peptides » CD 8+ T Cell
- 17. MHC II +peptides » CD 4+ T CellSelf-MHC I restriction
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- 19. TWO PATHWAYS BASEDON ANTIGEN
- 20. Antigen presentation byclass I mhc
- 21. PMhc class iα2α1α3*α1, α2, α3 are the domains of α chain,45kDa* β2 microglobulin ,12kDa,small soluble domain* P->Peptide-binding site* T->Hydrophobic Transmembrane segment* ER.M->Endoplasmic reticulum membrane* C->Hydrophilic Cytoplasmic tailβ2ER.MTC
- 22. α-chainEncoded by HLA-A,B,CgenesConsist of carboxyl-terminal short domain, transmembrane hydrophobic region,extracellular domain,aminoterminal signal peptideα-chain consists of α1,α2,α3 domainα1 and α2 forms a groove for the peptide-binding site
- 23. β2-microglobulinInteracts non-covalentlywith α3 domainEncoded by highly conserved gene located on a different chromosomeRequired for the expression of Class I molecules on cell membrane
- 24. ANTIGEN PRESENTATION BYMHC I4.Presenting to CD8+T cells1.Processing of endogenous Ag2.Transporting of antigen peptide into ER3.Peptide loading of class I MHC molecules
- 25. 1.PROcessing of endogenousAntigen20SEndogenous antigens are degraded by Proteasome(26S)Consist of 20S proteasome(a catalytic core) and 19S particle(a regulatory component)Degradation of protein requires ubiquitin molecule Cytokine(IFNγ) enhance the production of LMP2, LMP7 and MECL-1(LMP10) and replace β1,β5,β2 respectively to form IMMUNOPROTEASOMEβααβ19S
- 26. Ubiquitination of proteinUbE1ATPUbADP+ PiE1Ub-UbiquitinE1-Ubiquitin-activating enzymeE2-Ubiquitin-conjugating enzymeE3-Ubiquitin ligaseE2UbUbE1UbE3UbUbProteasomeUbPeptidesPolyubiquitinated protein
- 27. 2.Transporting of antigenpeptide into erTAP( Transporter associated with antigen processing)TAP2TAP1Consisting of TAP1 and TAP2ATP dependent transporterSelective transporting (8-11aa)
- 28. HydrophobictransmembranedomainLumen of ERPeptideERmembraneTAP-1TAP-2CytosolATP-binding cassette(ABC) domainPeptide antigensfrom proteasomeTransporters associated with antigen processing (tap1 & tap2)
- 29. PeptideTAP-1TAP-2Endoplasmic reticulum3.Peptide loadingof class I mhc moleculesNascent class I chainClass I MHCERP57β2-MCalnexinTapasinCalreticulin2-M binds and stabilises floppy MHCTapasin, calreticulin,ERP57, TAP 1 & 2 form a complex with the floppy MHCCalnexin bindsto nascentclass I chainUntil 2-M bindsCytoplasmic peptides are loaded onto the MHC molecule and the structure becomes compactβ
- 30. 4.Presenting to cd8+tcellsTc CellTCRAntigen peptide-class I MHC molecules presented on cell membrane by exocytosisPα2CD8α1α3β2C.MTC
- 31. Antigen presentation byclass ii mhc
- 32. 1. Capture ofexogenous antigen2. Processing of antigen3. Synthesis and transportation of class II molecule4. Association of processed peptide with MHC II5. Presenting to CD4+ T cellsEXOGENOUS OR ENDOCYTIC PATHWAY
- 33. Endocytosis Phagocytosis Pinocytosis Receptor mediated endocytosisForm Endosome CAPTURE OF EXOGENOUS ANTIGEN
- 34. Processing of antigenTakesplace in endosome(MIIC/CIIV) and lysosomeProtease – Cathepsin cleaves peptides from ProteinCell surfaceEndosomePeptides in endosome
- 35. Mhc ii moleculeα1β1MHC II is synthesized in ERFolding and assembly is aided by ER resident chaperon- calnexin INVARIANT CHAIN ( Ii ) Ii is a trimer ,each binding to newly formed MHC IITransport to GA through ER vesicle Fusion with MIIC containing HLA-DM ,cathepsin Sα2β2
- 36. Association of processedpeptide with MHC IIInvariant chain degradation leaving CLIP by proteolytic enzyme Cathepsin SReplacement of peptide in place of CLIP by HLA -DM
- 37. Presenting to CD4T cellsFormed peptide-MHC molecule is presented on surface of APC TCR binds with α1,β1 of MHC II and peptide
- 38.