T cell receptor activation 1

Question 1

true or false- t cells are not involved in most major pathological disorders?

Answer 1

false

Question 2

When does activation of the TCR occur?

Answer 2

when it binds to antigen-bound MHCs on the surface of an antigen presenting cell

Question 3

T or F- the TCR only interacts with the MHC?

Answer 3

False! both antigen and MHC

Question 4

Does there only need to be one interaction of TCR and antigen/MHC?

Answer 4

No– maybe as low as 10-20. naive t cells take more, primed less.

Question 5

MHC class I molecules are loaded with peptides from what compartment?

Answer 5

intracellular….dentritic cells are the exception an can also load them from extracellular sources

Question 6

Where are MHC class II molecules loaded with peptide from?

Answer 6

extracellular

Question 7

Where is the MHC II protein waiting?

Answer 7

in the lysosome

Question 8

Where is the MHC 1 protein waiting?

Answer 8

In the ER

Question 9

Which MHC binds short peptides?

Answer 9

MHC I…8-9 amino acids

Question 10

MHC has how many subunits?

Answer 10

2…alpha-chain binds the antigen,

beta2-microglobulin stabilizes the complex

Question 11

Where are proteins fragments that are loaded onto MHC I proteins coming from?

Answer 11

Immunoproteasome

Question 12

What is alpha chain MHC I bound to before beta chain is attached?

Answer 12

calnexin—after beta attaches calnexin releases

Question 13

What does MHC I alpha:beta complex bind to in ER?

Answer 13

complex of chaperone proteins (calreticulin, ERp57) and TAP via tapasin.

Question 14

What protein delivers peptide fragments to the ER?

Answer 14

TAP–after peptide binds it is able to complete folding and is released from complex and transported to cell membrane

Question 15

What are the only cells capable of loading MHC class I with endocytosed extracellular sources?

Answer 15

dendritic cells through cross presentation and is critical for ability of dendritic cells to activate naive CD8 T cells

Question 16

What do dendritic cells need to be activated by to be capable of cross presentation?

Answer 16

CD4 T cells—referred to as licensin

Question 17

cross presentation exogenous proteins make it to the cytosol via what complex?

Answer 17

Sec61 complex

can also happen through gap junctions and peptides generated on other cells

Question 18

Which subunit on MHC II binds the antigen?

Answer 18

alpha and beta— think of it this way…two subunits needed to bing the larger peptides that MHC II binds (12-20)

Question 19

What blocks the binding of proteins originally in the MHC II molecule? What happens to it?

Answer 19

invariant chain–it gets cleaved in the acidified endosomes, leaving a short peptide fragment CLIP bound…CLIP still blocks

Question 20

What binds to MHCII to release CLIP?

Answer 20

HLA-DM

Question 21

How are antigens from pathogens loaded on MHCII? non-specific antigens? intracellular antigens?

Answer 21

phagocytosis, macropinocytosis, autophagy

Question 22

What cells are MHCI molecules expressed on it?

Answer 22

all nucleated cells in the body and activates CD8 tcells

Question 23

What cells are MHC II molecules found?

Answer 23

antigen presenting cells-activate CD4 Tcells which control adaptive immune responses

Question 24

What chromosome contains the MHC locus?

Answer 24

6—200 genes. There are many alleles for each MHC class.

Question 25

Which MHC class has the highest number of alleles?

Answer 25

MHCI because they encode the entire peptide binding cleft— HOWEVER MHCII HAS THE HIGHEST DIVERSITY DE TO RANDOM RECOMBINATION OF ALPHA AND BETA

Question 26

What is it when you have multiple alleles for the same gene?

Answer 26

polymorphism

Question 27

What is when you have multiple genes with the same function?

Answer 27

Polygenic

Question 28

Why is MHC large diversity needed?

Answer 28

to increase repertoire of bound peptides

Question 29

The particular combination of MHC alleles on a single chromosome is called? How are they inherited?

Answer 29

MHC haplotype- and are inherited as a single gene

Question 30

T-F MHC haplotype is still evolving?

Answer 30

True–mutations and gene conversions

Question 31

The majority of the MHC diversity is localized where?

Answer 31

peptide binding clefts

Question 32

T-F certain haplotypes have bee linked to increased risk of autoimmune disorders?

Answer 32

True- Diabetes, hepatitis, thyroiditis, graves disease, coeliac disease, lupus, myasthenia gravis

Question 33

What transplantation types are matched?

Answer 33

bone marrow and kidney

Question 34

Host CD8 T cells can react strongly to what from donors?

Answer 34

mismatched MHC I present on dendritic cells

Question 35

type 2 bare lymphocyte disease has defects in TF for what MHC class?

Answer 35

MHC II–they have reduced numbers of CD4 T cells

Question 36

Patients with type 1 bare lymphocyte disease have defects in what?

Answer 36

TAP1, TAP2 or Tapasin

Question 37

What do super antigens bind to? what does it induce?

Answer 37

TCR and MHC—> induces the antigen independent atypical activation of T cells (some up to >40%) resulting in cytokine release

Question 38

What does cytokine release following super antigen binding lead to?

Answer 38

systemic toxicity and immune suppression

Question 39

T or F–can some viruses produce proteins that reduce MHC I expression

Answer 39

True for MHC I expression—viruses are intracellular

Question 40

Viral evasions U56 and ICP47 block what?

Answer 40

TAP peptide transporter

Question 41

Adenovirus protein E19 competes with what?

Answer 41

tapasin and inhibits peptide loading

Question 42

mK3 protein of murine gamma herpes virus does what?

Answer 42

E3-ubiquitin ligase targeting class I for degradation by proteosome

Question 43

How does the body combat suppression of MHC class I?

Answer 43

NK cells recognize cells that have low expression of MHC class I and kill them (release granules and trigger apoptosis)–mechanism due to fact that NK cells have receptors that recognize MHC class I and binding suppresses the NK action on them