Lecture 6 Adaptive Immunity - Antigen Presentation

Question 1

How are mature naive T cells activated?

Answer 1

antigen presentation by APC

• TCR recognizes self MHC /antigen combination
• APC is usually a DC that uses either MHC I (CD8) or II (CD4)

Question 2

What is significant about professional APCs?

Answer 2

can present with either MHC I or MHC II

Question 3

What does MHC stand for? What is another name for it?

Answer 3

Major Histocompatibility Complex = transplant compatibility

-also known as Human Leukocyte Antigen (HLA) = WBC function

Question 4

What kind of cells can express MHC I or MHC II molecules?

Answer 4

MHC I

• alpha chain+B2 microglobulin
• can be expressed by all nucleated cells
• erythrocytes not nucleated

MHC II

• alpha chain+beta chain
• professional APCs are DCs, Macrophages, B cells and can also express MHC I

Question 5

What are MHC/HLA loci?

Answer 5

encode different versions of alpha and beta chains to make different peptide binding sites

-creates variability in MHC presentation

Question 6

How are genes inherited from each parent?

Answer 6

As halotypes from each parent

• the alleles are co-dominant and expressed equally
• only results in slight variations in MHC antigen binding sites

Question 7

How do T cells tell whether an antigen presented is endogenous or exogenous?

Answer 7

MHC is used to present peptide antigens to T Cells

Peptides are loaded on 1 of 2 different classes of MHC based on ORIGIN of antigen

Endogenous Antigens

• synthesized inside cell during viral infection
• loaded onto MHC I

Exogenous Antigens

• englufed by phagocytic cells and loaded onto MHC II
• virus can be exogenous too if phagocytosed outside of cell

Question 8

What are the steps of the endogenous pathway?

Answer 8

1. Tag abnormal intracellular proteins in cytosol with Ubiquitin
2. Tagged proteins are shuttles to enzyme complex called proteasome which shreds protein into peptides
3. Peptides are transported by TAP into RER lumen for MHC I loading
4. RER proteins ERp57, calnexin, tapasin, calreticulin stabilize MHC I complex (alpha chain+B2 microglobulin) for loading
5. ERAP processes peptides to optimal size for peptide-binding groove of MHC I
6. Peptide loaded on MHC I and complex transported to cell membrane for presentation

Question 9

What are the steps of the exogenous pathway?

Answer 9

1. Extracellular antigens (eg. bacterial antigens) are phagocytosed/endocytosed
   - no ubiquitin and antigen always in vessicle
2. Digestion in phagosome/endosome creates peptides
3. Vessicles containing peptides fuse to vessicles from golgi apparatus containing MHC II
4. The MHC II in golgi vessicle stabilized by invariant chain which blocks binding site from peptides
5. Invariant chain digested by pH drop and formed into CLIP which is exchanged for peptides to bind MHC II
6. MHC II/peptide complex transported cell membrane

Question 10

Explain

Answer 10

Question 11

What are the APCs with MHC II?

Answer 11

Thymic Epithelial Cells

-positive and negative selection of immature T Cells

DCs and Macrophages (professional APCs)

-activate and mature naive CD4 T cells

B Cells (professional APCs)

-become activated by T_H Cells

Question 12

What are the APCs with MHC I?

Answer 12

Thymic Epithelial Cells

-positive and negative selection of immature T Cells

DCs and Macrophages (professional APCs)

• activate and mature naive CD8 T cells
• can use Cross Presentation

All Nucleated Cells

-target cells for cytotoxic response