A9 Antigen Presentation

Question 1

Atg Presentation on CD1

Answer 1

Presentation of foreign and self lipid components

Human: CD1a-CD1c, CD1d and CD1e peptids
Mouse: CD1d1, d2
Horse: 13 CD1s

Structural similarity to MHCI
• Heterodimer with β2 microglobulin • Bindind site larger than in MHCI

Presence
• APC, B cells, intestinal epithelium • Most actively on DC

CD1 restricted T cells • (CD4+, CD8+, CD4-8-) both Th1 and Th2

Question 2

MHC1 Antigen Presentation:

Answer 2

HC1 Antigen Presentation:
• Deliver short peptides to the cell surface to be recognized by Cytotoxic T-lymphocytes.
• The origin of these peptides is endogenous or intracellular.
• Cross presentation occurs when exogenous antigens are also presented by MHC I.
• Steps: e.g. virus infection
(1) Virus DNA/RNA enter the infected cell and starts producing viral proteins in the cytoplasm
(2) Viral proteins are taken up and digested in proteasomes into protein fragment (8-15AA long)
(3) TAPs (Transporters associated with Antigen Presentation) transport the protein fragment to rough ER
(4) The A- and B-chain of the MHC1 molecule is translocated into the ER membrane near the TAP, and the protein fragment bind to the protein binding site
(5) The MHCI-peptide complex moves to the cell surface via the Golgi apparatus, and finally situates on the cell membrane to be recognized by T-cells
(6) Both TCR receptors and CD8 co-receptor recognize the MHCI-peptide complex

Question 3

MHC2 Antigen Presentation:

Answer 3

• Extracellular proteins are endocytosed, digested in lysosomes and bound by the class II MHC molecule before migrating to the plasma surface where they are expressed.
• The origin of these foreign proteins is extracellular or exogenous.
• Steps: e.g. bacterial infection
1. APC internalizes the bacteria into an endosome (vesicle)
2. Fusion of endosome and lysosome into endolysosome
3. Digestion of bacteria into small peptide fragments
4. Synthesis og MHCII molecule in rough ER
5. Invariant chain binds to the MHCII molecule, this stops self-proteins from rER to bind with MHCII, and this MHCII-invariant chain complex moves to Golgi apparatus and then to a vesicle
6. When in the vesicle, only a small fragment of the invariant chain is left, called CLIP. The vesicle and the endolysosome fuses
7. The CLIP dissociates from MHCII and the peptide from the bacteria (11-15AA long) binds instead
8. The vesicle moves to the cell surface and the new MHCII-peptide complex attaches on cell membrane
9. Both TCR receptors and CD4 co-receptor recognize the MHCII-peptide complex