Adaptive immunity- antigen processing and presentation, dr. hudson

Question 1

In a viral infection, _ made by b cells can neutralize extracellular virus particles, but the source of the virus must be eliminated by _

Answer 1

antibodies, the humoral (b cell) response

T cells

Question 2

An effective immune system has to devise a system to sample both the _ and _ compartments.

Answer 2

vacuolar (injested bacterial material), cytoplasmic (where viruses would put their product protein)

Question 3

Peptide fragments are “presented” to T cells on _ molecules in a process called _ _

Answer 3

Class 1 or class 2 MHC

antigen presentation

Question 4

Outside of the cell is sampled by class _ MHC, inside of a cell (cytoplasm) is sampled by class _ MHC

Answer 4

outside- class 2, inside, class 1

Question 5

Concepts underlying class 1 MHC antigen presentation to T cells

1. proteins must be _ _ _
2. _ must occur to generate peptides of the appopriate size
3. peptides must be _ to class 1 MHC molecules
4. Peptides must _ to class 1 MHC molecules
5. Peptides must be displayed to _ in the contect of class 1 MHC molecules

Answer 5

tagged for destruction

proteolysis

delivered

bind

T cells

Question 6

Small molecule (8kDa) added to lysine residues on proteins destined for degradation.

Answer 6

ubiquitin

Question 7

What kinds of peptides are presented on class 1 MHC molecules?

Answer 7

all were 9 peptides in length, ending in a hydrophobic (valine or isoleucine)

Question 8

3 types of protease activity associated with the proteosome. Caspase-like, trypsin-like, and chymotrypsin like. Chymotrypsin like cleaves after _ amino acids

Answer 8

hydrophobic

Question 9

a protective cytokine usually associated with a virus infection

upregulates proteosome subunits called LMPs, which increase production of peptides suitable for antigen presentation (chymotrypsin activity)

Answer 9

IFNγ

(interferon gamma)

–>immunoproteosome

Question 10

Proteosome cap recognizes and removes_, but then the protein must be _ to go into the proteosome, which is located in the cytoplasm.

Peptides from the proteosome go into the ER via the _ transporter and bind to the newly synthesized _

Answer 10

ubiquitin chain

unfolded

TAP (Transporter associated with Antigen Processing)

Class 1 MHC molecule

Question 11

TAP

Encoded in _ gene

_ membrane spanning domain integral membrane proteins

One substrate: _, ending with _ _ _ _ are favored

Size range: _-_ amino acid residues

Answer 11

MHC (major histocompatibility complex) on chromosome 6

12

peptides ending with L I V M are favored

6-15

Question 12

Class 1 MHC molecule has size restriction, it accepts residues that are _-_ residues long

The Class 1 MHC assembles with a light chain called _

Loading complex includes _ molecule which is thought to tether the newly synthesized class 1 MHC molecule to TAP, keeping it in close proximity to incoming peptides

Answer 12

8-10

B2m (beta2 microglobulin)

tapasin

Question 13

T cell receptors (TCR) recognize the combination of _ + _

Answer 13

MHC + peptide

Question 14

“Education” of T cells in the thymus occurs during development.

Which types of t cells die and which do not?

Answer 14

The t cell that recognizes self peptide and mhc complex with high affinity dies, the t cell that does not have any affinity dies (death by neglect)

Weak/moderate affinity T cell receptors live to populate the periphery

Question 15

What is alloreactivity

Answer 15

the reactivity of T cells (or B cells) to non-self (allogenic) MHC class 1 or 2 molecules.

The ones that went to live on after thymic education had weak affinity, but if they come across foreign peptides inside of a self MHC or a foreign MHC (from translant) then the T cell will kill the target cell.

This is the reason for immediate transplant rejection

Question 16

Structure of class 1 MHC?

What is the “light chain”

What is the “heavy chain?

Where does the peptide sit?

What is the difference between Class 1 and Class 2 MC in structure?

Answer 16

B2m

a1,a2, a3

Between a1 and a2

class 2 has two heavy chains and is encoded by two genes. Alpha chain and Beta chain. The class 1 MHC is coded by one gene.

Question 17

Class 1 peptides are _-_ residues

Class 2 peptides are _-_ residues, can be longer

Answer 17

8-10

10-16, can be up to 30

Question 18

Some differences between class 1 and class 2 pressentation to T cells.

Which one needs to tag proteins for destruction?

Which class is used for engulfed pathogens?

Which class must have peptides delivered to it?

Answer 18

Class 1 MHC, these are for the inside of the cell

Class 2 MHC is used for englufed

Class 1, using the TAP

Question 19

Which class of MHC…. peptides must be displayed to *CD8 T CELLS* in the context of MHC molecules?

Which class of MHC… peptides must be displayed to *CD4 T CELLS* in the context of MHC molecules?

Answer 19

Class 1

Class 2

Question 20

Loading of peptide occurs in the ER for this class of MHC

Loading of peptide occurs in the endocytic compartment for this class of MHC

Answer 20

Class 1

Class 2

Question 21

Tagging of proteins for destruction happens with this class of MHC

Answer 21

Class 1 MHC

Question 22

proteolysis for class 2 does not require tagging to the proteosome, but rather requires delivery to the _ where _s at a pH5 will chop them up

where it will also be loaded and displayed to _

Answer 22

Lysosome, antigen undergoes proteolysis into peptides, mediated by lysosomal proteases (cathepsins)

CD4 T cells

Question 23

Class 2 molecules are made in the ER (like class 1) but they do not bind peptides there because of _

Answer 23

Invariant chain (Ii)

Question 24

scaffold, stabilizer to MHC 2

Barrier to peptides in the ER

has “Zip code” to MIIC (LL) (sorting signal)

Answer 24

invariant chain (Ii)

Question 25

What is the purpose of the invariant chain?

Answer 25

forms a trimer with 3 class 2 MHC molecules and 3 invariant chains.

scaffold, stabilizer to MHC 2

Barrier to peptides in the ER

has “Zip code” to MIIC (LL) (sorting signal)

Question 26

What happens when Invariant chain and MHC2 trimer gets to the lysosome?

Answer 26

Cleavage by lysosomal enzymes leaves a short peptide fragment, CLIP, bound to the class 2 molecule.

Question 27

What molecule is responsible for dislodging the CLIP peptide (remnants of invariant chain (Ii) from the class 2 molecule?

Answer 27

HLA-DM

Question 28

Self peptides (can/cannot) be presented by class 2 molecules

Answer 28

Can, anything targeted to the lysosome. Tissue debris from tissue damage, macrophages engulf self and present these peptides to CD4-t cells

Question 29

Antigen in the periphery is englufed by _ cells that activate T cells

Answer 29

dendritic cells. They migrate to a lymphoid organ, where naive b and T cells reside. This is where T cells first see the antigen. To activate virus specific CD8+ T cells, in the lymph node, if a particular CD8 T cell can bind tightly to that antigen/ MHC class 1 complex, it becomes activated to proliferate.

Question 30

If dendritic cell ENGULFS virus, then it will display class _ MHC complex and will interact with CD_+ T cells

If it is INFECTED by virus proteins, it will display class _ and will interact with CD_+ T cells

Answer 30

engulfed- Class 2, Cd4

infected by- Class 1, Cd8

Question 31

Which cells can have cross presentation to T cells? if it engulfs a virus but isnt infected by a virus, it will present *Class 1* as well as Class 2

Answer 31

dendritic cells, a specialized antigen presenting cell

Question 32

Describe cross presentation

Answer 32

The specialized antigen-presenting cell’s ability to present Class 1 and class 2

Question 33

Antigen presentation molecule that is similar to class 1 and class 2 MHC molecules in structure (also has B2m and have similar shaped groove for binding antigen) but instead of peptides they bind lipid antigens.

Answer 33

CD1 molecules

Question 34

Cd1 molecules bind

Answer 34

lipid antigens

Question 35

Antigen presenting cells have _, _, and _ expression.

Other cells, like liver cells, only have _

Answer 35

Class 1, 2, CD1

Class 1

Question 36

CD1 specific T cell that express classical T cell receptors (alpha/beta) and recognize lipid antigens

Answer 36

NK-T cells

Question 37

Specialized antigen presenting cells (3)

Answer 37

B cells

Dendritic cells

Macrophages

Question 38

class of MHC molecule expressed on all nucleated cells

Answer 38

MHC 1

Question 39

class of molecule expressed only on specialized antigen presenting cells

Answer 39

MHC2

Question 40

MHC 1 molecules present peptides derived from _ proteins to CD_T cells

Answer 40

cytosolic, cd8

Question 41

mhc 2 molecules present peptides derived from _ proteins to CD_ tcells

Answer 41

intravesicular

4

Question 42

_ is essential for stable expression of MHC molecules at the cell surface

Answer 42

peptide binding