Antigen Capture And Presentation To Lymphocytes

Question 1

Which cell does MHC class I talk to?
Class II?

Answer 1

CD8 (cytotoxic T cell) and Class I = 8

CD4 (helper T cell) and class II= 8

Question 2

What does MHC class I pathway display?
Class 2?

What type of antigen is displayed by MHCs?

Answer 2

Class 1 displays cytoplasmic (endogenous) antigens (self)

Class 2 displays exogenous (engulfed) proteins (not self) endisomal/lysosomal

PROTEINS

Question 3

List the 6 features of peptide binding to MHC molecules and their significance

Answer 3

1) broad specificity: many different peptides can bind to same MHC molecule
2) each MHC molecule displays 1 peptide at a time: each T cell responds to a single peptide bound to a MHC molecule
3) MHC molecules bind only peptides: MHC-restricted T cells respond to only protein antigens, not to other chemicals
4) peptides are acquired during intracellular assembly: class 1&2 MHC molecules display peptides from different cellular compartments
5) stable surface MHC molecule expression requires bound peptide: only peptide loaded MHC molecules are expressed in cell surface for recognition by T cells
6) very slow off rate: MHC molecule displays bound peptide for long enough to be located by T cell

Question 4

What captures blood borne antigens and where do they go?
What collects antigens from epithelial and connective tissue?
Where are antigens always concentrated?

Answer 4

Antigen presenting cells capture blood borne antigens, they go to spleen

Epi and ct antigens collected by lymph node

Concentrated in secondary lymph tissue

Question 5

Can T cells bind to free antigens?

How can T cells recognize antigens/ what do innate cells use to show antigens to T cells?

Answer 5

No, they must be shown them

Innate cells (usually dendritic) use MHCs to present antigens to T cells. The T cell must recognize both the antigen and the MHC to activate. T cell moves on if it doesn’t recognize BOTH

Question 6

What are the three professional antigen presenting cells?

Answer 6

Dendritic cells
Macrophages
B lymphocytes

Question 7

Which cells present to CD8 (cytotoxic T cells)?
To CD4 (helper T cells)?

Answer 7

All nucleated cells (all but RBC) can present class 1 MHC peptides to CD8+ cytotoxic T cells, which are endogenous proteins- includes prof antigen cells too!

Only professional antigen presenting cells (dendritic, macrophages, B lymphocytes) can present class 2 MHC peptides to CD4+ helper T cells, which are all exogenous proteins

Question 8

What are MHC molecules?

Answer 8

Membrane proteins on APCs that display peptide antigens for recognition by t lymphocytes

Question 9

Overview antigen capture and presentation by dendritic cells

Answer 9

1) DC in epidermis, phenotypically immature
2) antigen capture by DC–> TLR ligands and cytokines
3) activation of DC
4) migration of DC (via afferent lymphatic vessel)
5) maturation of migrating DC
6) mature DC presents antigen to naive T cell in lymph node

Question 10

Explain the structure of MHC class 1 vs class 2 molecules

Answer 10

Class 1: 1 membrane bound protein chain (a1,2,3 domains), b2m accessory chain for structure, peptide binding cleft 8-11 aa

Class 2: 2 mem bound chains (a2&b2), then each half makes half of peptide binding groove, 10-30 aa

Question 11

What enzymes are responsible for peptide generation in class 1 vs. class 2

Answer 11

Class 2: endosomal and lysosomal proteases

Class1: cytoplasmic proteasome

Question 12

Site of peptide loading of MHC class 1 vs. 2?

Answer 12

Class 1: ER

Class 2: specialized vesicles

Question 13

What are the 4 basic concepts to keep in mind about antigen presentation?

Answer 13

1) translation occurs in cytoplasm–> viral and intracellular bacterial antigens are in cytoplasm
2) excreted proteins or those bound for cell surface are processed in ER and shipped through Golgi
3) endocytotic vesicles internalize cells/cell parts, which have low pH and proteases
4) MHC molecules are in excess to antigen

Question 14

Class 1 vs. class 2 MHC pathways?

Answer 14

Class 1: proteasome breaks down endogenous proteins> microbial proteins also caught> small peptides go to TAP, which pumps proteins into ER> MHC class 1 waiting in ER> specific peptide bonds> ship through Golgi >to surface for a while then recycled, never lets go of peptide

Class 2: exogenous antigen, invariant chain (protects peptide binding groove), embedded portion cut off–> CLIP peptide left (protein portion of invariant chain), HLA-DM (gets MHC to release CLIP so it can bind antigen)

Question 15

What to keep in mind about dendritic cell cross presentation?

Answer 15

They can present both pathways to activate CD4 and CD8
Can take in entire cells (even our own)
They are dynamic
Do the vast majority of antigen presentation

Question 16

What is the advantage of all MHC genes being close to each other in genome?

Answer 16

Can be up/down regulated together easily

Question 17

How many versions of class 1 are there?
How many do we receive?
How many versions of class 2?
How many totAl versions do we get?
This is human population as a whole!

Answer 17

Class 2 has 3 versions: A, B, C
We get two of each (one per parent), so 6 total class 1, which is why transplants are so difficult
Class 2: 3 versions for each membrane bound protein chain, so 2 genes per variation= minimum 6 class 2s (referring to alpha and beta together)
Total= 12

Question 18

Polymorphism vs polygeny?

Answer 18

Polygeny= versions of each gene (such as ABC of MHC class 1

Polymorphism= variance in each type/version (such as 559 variations of MHC class 1A

Question 19

Where does allergic variation affect which peptides can bind to the peptide binding groove?changes elsewhere?
Advantage of variation in terms of species survival?

Which chain of class 2 contributes to variability?

Answer 19

Variations in peptide binding groove, elsewhere is just structural changes

How sub population of humans can survive new pathogens (think zombie apocalypse), diversity is important

Beta chain of class two

Question 20

Three important properties of MHC molecules and genes

Answer 20

Codominant expression: high variation in peptide presenting

Polymorphic genes: different individuals can respond to different microbial peptides