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http://www.blink.biz/immunoanimations/
http://cmgm.stanford.edu/theriot/
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How do T cells recognize antigens?
Antigen ProcessingAntigen PresentationAntigen Presenting Cell (APC)Professional APC
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MHC class I communicates with Tc cells
MHC I = Intracellular
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IR to Extracellular Pathogens(CD4-MHC II)
1. Antibodies needed
2. Pathogen recognition/internalization by professional APCs
a. B cellsb. Macrophagesc. Dendritic cells
3. Phagolysosome degrades proteins to peptides
4. Peptides:MHC II complex transported to surface
5. Professional APC contacts CD4 T cells
6. CD4 TH cells secrete cytokines to signal B cell maturation
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MHC class II communicates with TH cells
MHC II = Extracellular
Receptor mediated Internalization
Phagocytosis
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IR to Intracellular Pathogens(CD8-MHC I)
1. Antibodies ineffective
2. Pathogen replicates in the cell and proteins are degraded in the cytoplasm of the cell
3. Peptides are transported into ER and bind MHC I and transported to the surface
4. MHC I expressing cells present to CD8 T cells
5. CD8 T cells (cytotoxic T cell, CTL) kills host cell
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Figure 3-11
Lymph node
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Structures involved in MHC Presentation
TCR
CD4 and CD8
MHC1 and MHCII
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T cell Co-Receptors
Binds MHC I
Binds MHC IITH
TC
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Figure 3-13 part 1 of 2
Variable
Invariant
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CD8-MHC I CD4-MHC II
CD8-3CD4-2
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Figure 3-15Closed Open
8-10 amino acids 13-25 amino acids
Degenerate binding specificity
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Figure 3-16
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Proteosome=Shredder
Transporter associated with antigen processing
Peptide Degradation and Transport
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Chaperones
CalnexinCalreticulinTapasin
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Bare lymphocyte syndrome- TAP deficiency
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Figure 3-19
Acidic process
Golgi Transport
Vacuolar Transport
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CLIP - class II-associated invariant-chain peptide
Prevention of Peptide:MHC II formation in ER
Invariant Chain (li) - Prevent peptide binding in ER - Deliver to vesicles
HLA-DM - Release of CLIP, peptide loading
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Figure 3-21 part 2 of 3
TCR binds MHC and peptide
CDR3 binds peptideCDR2 binds MHCCDR1a binds N-terminalCDR1b bind C-terminal
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• Cytokines can regulate expression
• Interferon induces MHC II expression
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T-cell Diversity- Recombination- Structure of TCR and associated molecules- Immunodeficiency diseases
Antigen Processing and Presentation- Intracellular vs Extracellular- MHC structure