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How do T cells recognize antigens?

Antigen ProcessingAntigen PresentationAntigen Presenting Cell (APC)Professional APC

MHC class I communicates with Tc cells

MHC I = Intracellular

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

MHC class II communicates with TH cells

MHC II = Extracellular

Receptor mediated Internalization

Phagocytosis

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

Figure 3-11

Lymph node

Structures involved in MHC Presentation

TCR

CD4 and CD8

MHC1 and MHCII

T cell Co-Receptors

Binds MHC I

Binds MHC IITH

TC

Figure 3-13 part 1 of 2

Variable

Invariant

CD8-MHC I CD4-MHC II

CD8-3CD4-2

Figure 3-15Closed Open

8-10 amino acids 13-25 amino acids

Degenerate binding specificity

Figure 3-16

Proteosome=Shredder

Transporter associated with antigen processing

Peptide Degradation and Transport

Chaperones

CalnexinCalreticulinTapasin

Bare lymphocyte syndrome- TAP deficiency

Figure 3-19

Acidic process

Golgi Transport

Vacuolar Transport

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

Figure 3-21 part 2 of 3

TCR binds MHC and peptide

CDR3 binds peptideCDR2 binds MHCCDR1a binds N-terminalCDR1b bind C-terminal

• Cytokines can regulate expression

• Interferon induces MHC II expression

T-cell Diversity- Recombination- Structure of TCR and associated molecules- Immunodeficiency diseases

Antigen Processing and Presentation- Intracellular vs Extracellular- MHC structure