Antigen Capture and Presentation

Question 1

What are T cells activated by?

Answer 1

Antigen presenting cells

Question 2

What do APCs do with antigens?

Answer 2

They capture them in tissues and transport them to peripheral lymphoid tissues where lymphocytes are concentrated to present the antigens to T cells

Question 3

What are the most common cells to present antigens?

Answer 3

Dendritic cells

Question 4

Why are co-stimulatory molecules important?

Answer 4

They are another way of regulating responses and are dependent on the pathogen being present so that we don’t develop autoimmunity

Question 5

What is the role of CB3?

Answer 5

It is involved in signal transduction, not recognition

Question 6

What types of pathogens does MHC-1 present and to what type of T-cell?

Answer 6

Intracellular pathogens to CD8+ T cells

Question 7

What types of pathogens does MHC-2 present and to what type of T-cell?

Answer 7

Extracellular pathogens to CD4+ T cells

Question 8

What is the MHC locus?

Answer 8

A collection of genes found in all mammals that code for MHC molecules
The locus contains two sets of highly polymorphic genes (class I and II)

Question 9

What is polymorphism?

Answer 9

Multiple alleles of a gene within a population

Question 10

How does MHC interact with peptides?

Answer 10

Most MHC peptide binding clefts have pockets
Sided chains of 2 or 3 amino acids of antigenic peptides fit into the MHC pockets and anchor the peptide in the MHC peptide-binding cleft
Additional amino acid resides of the antigenic peptide extend upwards and are recognized by TCR

Question 11

Why do MHC molecules have broad specificity?

Answer 11

Because any given MHC can present any peptide with the correct anchor reside, allowing a small number of MHC molecules to display a large array of peptide antigens

Question 12

How are MHC-peptide complexes stable?

Answer 12

Peptides remain on display for up to days which maximizes the likelihood of encountering the correct T cell

Question 13

Which cells express class II MHC?

Answer 13

Dendritic cells, macrophages, B cells

Question 14

Which cells express class I MHC?

Answer 14

All nucleated cells

Question 15

What is the structure of class 1 MHC?

Answer 15

An alpha chain noncovalently linked to a beta2-microglobulin chain

Question 16

What do alpha1 and alpha2 domains form in a class 1 MHC?

Answer 16

A peptide binding groove that holds peptides of 8-11 amino acids

Question 17

How does the TCR interact with the MHC molecule?

Answer 17

The TCR sits down on top of the MHC molecule and contacts residues extending up and out of the peptide binding groove on the antigenic peptide

Question 18

Where are polymorphic residues located on class 1 MHC molecules?

Answer 18

in the alpha1 and alpha2 domains

Question 19

What is the role of the alpha3 domain on class 1 MHC molecules?

Answer 19

It is invariant and contacts only the T cell CD8 co-receptor
Only CD8 T cells respond to class 1 MHC-bound antigens

Question 20

What is the role of TAP in antigen processing?

Answer 20

TAP binds peptides and transports them from the cytosol into the lumen to bind MHC

Question 21

What happens if a class I molecule stably blinds a microbial peptide?

Answer 21

The complex is sent to the cell surface via the Golgi and exocytic vesicles

Question 22

What does the class I pathway respond to?

Answer 22

Intracellular microbes

Question 23

Where do class I MHC molecules present intracellular microbes?

Answer 23

On the surface of all nucleated cells

Question 24

What recognizes the class I MHC-peptide complex?

Answer 24

CD8 T-lymphocytes that upon activation will differentiate into cytotoxic T lymphocytes to kill infected cells

Question 25

What is the structure of class II MHC molecules?

Answer 25

An alpha chain noncovalently linked to a beta chain

Question 26

What do the alpha1 and beta1 domains on a class II MHC molecule form?

Answer 26

A peptide binding groove that holds peptides of 10-30 amino acids

Question 27

What residues does the TCR contact from class II MHC molecules?

Answer 27

Residues of the antigenic peptide that extend up out of the peptide binding groove

Question 28

Where are the polymorphic residues of class II MHC located?

Answer 28

In the alpha1 and beta2 domains

Question 29

Which domain on class II MHC molecules is invariant?

Answer 29

The beta2 domain that contacts the T cell CD4 co-receptor
Thus, only CD4 T cells respond to class II presented antigens

Question 30

What does the class II pathway respond to?

Answer 30

Extracellular microbes

Question 31

What do CD4 T cells stimulate B lymphocytes to do?

Answer 31

Produce antibodies and phagocytes to ingest and destroy microbes

Question 32

What is the co-dominance of MHC molecules?

Answer 32

Both parental alleles are expressed equally
Each individual can express up to 6 different class I molecules and 10 to 20 different class II molecules

Question 33

What are the 5 features of peptide binding to MHC?

Answer 33

Each MHC molecule displays 1 peptide at a time
Broad specificity
Very slow off-rate
Stable expression requires peptide
MHC molecules bind only peptides

Question 34

What is the significance of MHC molecules displaying only one peptide at a time?

Answer 34

Each T cell responds to a single peptide bound to an MHC molecule

Question 35

What is the significance of broad specificity for peptide binding to MHC?

Answer 35

Many different peptides can bind to the same MHC molecule

Question 36

What is the significance of a very slow off-rate for peptide binding to MHC?

Answer 36

MHC molecule displays bound peptide for long enough to be located by a T cell

Question 37

What is the significance of why stable expression requires a peptide for MHC?

Answer 37

Only MHC molecules that are displaying peptides are expressed for recognition by T cells