Antigen Capture and Presentation to Lymphocytes

Question 1

What do BCRs recognize?

Answer 1

B Cell Receptors can recognize a variety of macromolecules in soluble form or cell-surface associated form

• Proteins
• Polysaccharides
• Lipids
• Nucleic Acids
• Haptens (small chemicals)

B Cell mediated humoral immune responses may be generated against many types of microbial cell wall and soluble antigens

Question 2

What do TCRs recognize?

Answer 2

T Cell Receptors recognize ONLY PEPTIDE FRAGMENTS of protein antigens

And only when these peptides are generated inside a host cell and then PRESENTED on the cell surface in association with specialized molecules called Major Histocompatibility Complexes (MHC)

T Cell mediated immune responses may be generated only against protein Ags that are either produced or taken up by host cells

NOTE: TCR can only recognize broken up (processed) into LINEAR (unfolded) PEPTIDES when displayed by Antigen Presenting Cells (APCs) in association with MHC molecules expressed on the APC cell surface

ONLY LINEAR SMALL PEPTIDES

Question 3

Which chromosome contains the HLA genes responsible for both MHC Class I and MHC Class II?

Answer 3

CHROMOSOME 6

Question 4

Genes for which immunologic protein are POLYMORPHIC?

Answer 4

HLA/MHC genes

Question 5

How many polymorphic chains are found on MHC I and MHC II?

Answer 5

MHC I has only 1 polymorphic heavy chain
- It is encoded by HLA-A, HLA-B, and HLA-C genes

MHC II has 2 dissimilar polymorphic polypeptide chains (alpha and beta)

• They are encoded by HLA-D genes:
• HLA-DP, HLA-DR, and HLA-DQ

The polymorphic chains are what form the binding groove for the MHC molecule.

Question 6

What is the difference in composition of the MHC I and MHC II?

Answer 6

MHC I has a single polymorphic heavy chain (Alpha chain) noncovalently attached to the NON-polymorphic Beta-2 microglobulin

MHC II has 2 polymorphic chains non-covalently attached to each other. A
- An Alpha chain and a Beta chain

Question 7

Do HLA genes show codominant expression?

Answer 7

YES

Both parental alleles of each MHC gene are expressed

This increases the number of different MHC molecules that can present peptides to T cells

Question 8

Which cells express MHC Class II molecules?

Answer 8

Professional Antigen Presenting Cells

• B Cells
• Dendritic Cells
• Macrophages

Question 9

Which cells express MHC Class I molecules?

Answer 9

ALL NUCLEATED CELLS (including APCs)
- RBCs do not express MHC

This means that APCs express both MHC I and MHC II

Question 10

Where do the peptides expressed within MHC Class I molecules come from?

Answer 10

Peptides presented in MHC I molecules are derived from Viruses or other INTRACELLULAR microbes that have infected the host cell.

Ag source is CYTOSOLIC

Question 11

What cells recognize MHC I molecules and what cells recognize MHC II molecules?

Answer 11

MHC I = CD8+ Cytotoxic T Lymphocytes

MHC II = CD4+ T Helper Cells

Question 12

Where do the peptides expressed within MHC II molecules come from?

Answer 12

Peptide antigens are taken from the phagocytosis of EXTRACELLULAR pathogens by APCs

Ag source is from the Endosome/Lysosome (internalized from extracellular environment)

Question 13

What are TCRs looking for when presented an Ag?

Answer 13

TCRs simultaneously recognize the some amino acid residues on the presented peptide Ag as well as the residues of the MHC molecule that is displaying the peptide

Question 14

Which MHC molecule can accommodate longer peptides?

Answer 14

MHC II

Question 15

What is the function of HLA-DM?

Answer 15

HLA-DM is an editing mechanism that works to ensure the presentation of only the protein fragments most relevant for eliciting an immune response

• Causes dissociation of CLIP (Class II-associated Invariant Chain Peptide) from the peptide binding groove of MHC II
• Stabilizes and prevents degradation of the empty MHC II
• Facilitates the binding of Ag fragments to the open, stabilized binding groove

Question 16

What is the Class II MHC pathway in Professional APCs?

Answer 16

1) Uptake of EXTRACELLULAR proteins into vesicular compartments of the APC
2) Processing of internalized proteins in endosomal/lysosomal vesicles

3) Biosynthesis and transport of Class II MHC molecules to the endosome
- MHC syntehsized in ER, packaged in Golgi, delivered to endosome

4) Association of processed peptides with Class II MHC molecules in vesicles (via HLA-DM)
5) Expression of Peptide-MHC complexes on cell surface

Question 17

What is the Class I MHC Pathway?

Answer 17

1) Microbe produces proteins in the cytosol

2) Proteolytic degradation of proteins
- Microbe proteins are ubiquinated and destroyed in Proteosome

3) Transport of peptides from cytosol to ER
4) Assembly of peptide-MHC class I complexes in the ER
5) Packaging of peptide-MHC complex in golgi, then transport to cell membrane for expression

Question 18

What happens when a APC consumes an intracellular microbe (such as a virus)?

Answer 18

In this scenario, the APC will take the protein Ag from the ingested microbe from the Phagosome into the cytosol

This initiates the process of the Class I MHC pathway

This allows the APC to present the Ag to CD8+ T cells instead of CD4+ T cells

Recall that CD8+ T cells respond to intracellular microbes while CD4+ respond to extracellular

Question 19

How many alleles of Class II HLA molecules can a single person have at most?

Answer 19

6

Parental/Maternal pairs of HLA-DR, HLA-DP, and HLADQ

Question 20

What do activated Th1 cells do?

Answer 20

Th1 cells produce IFN-gamma

When Th1 cells are presented an antigen from Macrophages, they produce IFN-gamma, which signals the Macrophage to kill the microbe it has consumed

Question 21

What do activates Th2 cells do?

Answer 21

Th2 cells produce IL-4

When Th2 cells are presented an antigen from a B cell, they produce IL-4, which tells the B Cell to:

• Proliferate
• Mature into Plasma Cells
• Produce lots of antibodies
• Tells some to become memory cells