8. Antigen presentation to T lymphocytes

Question 1

why don’t B cells need antigen presentation

Answer 1

they secrete antibodies that look for pathogens

Question 2

where does antigen presentation to T cells take place in the body?

Answer 2

secondary (peripheral) lymph organs

Question 3

T cells recognize and respond to… NOT…

Answer 3

cell-associated antigens
soluble, cell-free antigens (role of B cells)

Question 4

properties of antigens recognized by T cells

Answer 4

most T cells recognize only short peptides
peptides they recognize depends on MHC restriction

Question 5

what is antigen processing

Answer 5

the generation of peptides from native proteins

Question 6

intracellular pathogens from the cytosol

Answer 6

transported to the ER and loaded onto MHC I
include viruses and certain bacteria
found in both somatic and immune cells
presented directly

Question 7

intracellular pathogens from vesicular compartments

Answer 7

involved in endocytosis and secretion
loaded onto MHC II so helper T cells can alert B cells

Question 8

characteristics of cytosolic pathogens

Answer 8

degraded in cytosol
bind to MHC I
presented to CD8 T cells
causes cell death of APC
found in somatic and immue cells

Question 9

characteristics of intravesicular pathogens

Answer 9

degraded in endocytic vesicles
bind to MHC II
presented to CD4 T cells
causes macrophage activation to kill intravesicular pathogen
restricted to immune cells

Question 10

characteristics of extracellular pathogens

Answer 10

degraded in endocytic vesicles of B cells
bind to MHC II
presented to CD4 T cells
causes activation of B cells to secrete Ig and eliminate extracellular pathogens

Question 11

what is cross-presentation of antigens

Answer 11

the ability of APCs to take up, process and present antigens from an outside source with MHC I to CD8 T cells
this cell itself is not infected
important in immunity against tumors

Question 12

what is cross-priming

Answer 12

the activation of naive CD8 T cells into activated cells by cross-presentation

Question 13

what is the autophagy pathway of pathogens

Answer 13

the delivery of cytosolic antigens for presentation by MHC II
deals with self antigens

Question 14

how are proteins degraded in the cytosol

Answer 14

carried out by the proteasome that has a 20S catalytic core and 2 19S regulatory caps
protein is ubiquitinated in the cytosol
ubiquitin chain is linked to K48 and recognized by the 19S cap, unfolded and chopped up into short peptides that can be presented on MHC

Question 15

what are TAP1 and TAP2

Answer 15

proteins that transport peptides in the cytosol to the ER before binding MHC I

Question 16

what is ERAP1

Answer 16

ER aminopeptidase associated with antigen processing in the cytosol
trims the amino terminus if it is too ling to bind MHC
its expression is increased by IFN-y stimulation

Question 17

mechanism of peptide processing and loading on MHC I molecules

Answer 17

partially folded MHC I alpha-chain binds calnexin
B2 microglobulin binds and calnexin is released
complex binds to calreticulin, ERp57 and TAP
cytosolic peptides created by protease are delivered to the ER by TAP
the peptide binds the MHC I molecule to complete its folding
MHC I is released from the TAP complex and exported to cell membrane

Question 18

which proteins make up the peptide loading complex for MHC I

Answer 18

calreticulin, tapsin, ERp57, TAP

Question 19

how are peptides that bind to MHC II generated

Answer 19

antigen is taken up from extracellular space via endocytosis
acidification of vesicles activates proteases to degrade antigen into peptide fragments
vesicles containing peptides fuse with vesicles that contain MHC II

Question 20

what is the invariant chain

Answer 20

a molecule that directs newly synthesized MHC II molecules to acidified intracellular vesicles

Question 21

how does the invariant chain bind MHC II

Answer 21

invariant chain (li) binds in the groove of MHC II
li is cleaved to leave a fragment bound to MHC II and to the membrane
further cleavage leaves a short peptide fragment (CLIP) bound to the MHC II molecule

Question 22

what facilitates the loading of antigenic peptides onto MHC II molecules

Answer 22

HLA-DM

Question 23

mechanism of peptide processing and loading on MHC II molecules

Answer 23

MHC II binds the invariant chain in the ER
invariant chain is cleaved leaving CLIP bound to the MHC II
the phagolysosome with the antigen peptide fuses with the MHC II vesicle
HLA-DM binds to MHC II, releasing CLIP
MHC II travels to cells surface

Question 24

what is different about how MHC I and II acquire the peptides they bind

Answer 24

• MHC I acquire peptides from cytosolic protein degradation via proteasome with TAP assisting peptide transport
• MHC II bind invariant chain which inserts CLIP. followed by cleavage in acidic endosomes

Question 25

diverse rolls of MHC II

Answer 25

activating macrophages
aiding B cell antibody production
regulating immune responses

Question 26

3 ways the diversity of antigen presentation by MHC attained

Answer 26

polygenic: several MHC I and II genes
polymorphism: many variants
codominance: expressed from both inherited alleles

Question 27

what does MHC polymorphism ensure

Answer 27

the population will not succumb to a new pathogen or a mutated one because at least some individuals can develop an adequate immune response to it

Question 28

MHC diversity is limited to…

Answer 28

the binding site - T-cell recognition of antigens is MHC restricted

Question 29

3 properties are affected by MHC polymorphism;

Answer 29

1. the range of peptide bound
2. the conformation of the bound peptide
3. the direct interaction of the MHC molecule with the TCR

Question 30

what is an exception to MHC presentation to T cells

Answer 30

non-peptide antigen presentation

Question 31

how are non-peptide antigens presented to T cells

Answer 31

non-classical class I molecules
CD1 family of proteins
MR1: MHC class I related protein