10 T cell receptor activation

Question 1

what is the key cell type that activates the CD4 and CD8 cells? How does it do it?

Answer 1

Key cell= dendritic cell

It uses MHC 2 or MHC1 bound to an antigen to activate it.

Question 2

T/F Each TCR recognizes one or a small number of antigens presented by the MHC complex.

Answer 2

True

The TCR interacts with both the antigen and the MHC.

Question 3

How many TCR/MHC interactions are required to activate the T cell? How many TCR’s are generally on a T cell?

Answer 3

10-20 TCR’s are sufficient to activate a T-cell

There can be up to one hundred thousand receptors on each cell.

Question 4

CD8 binds to? CD4 binds to?

Answer 4

CD8=MHC1

CD4=MHC2

Question 5

where do the majority of peptides come from that are presented on MHC 1 come from?

Answer 5

intracellularly.

The exception is with dendritic cells that can present MHC 1 with extracellular antigen.

Question 6

which 2 components make up the MHC 1 complex?

Answer 6

alpha(1-3), and beta 2 microglobulin

Question 7

what is the function on beta 2 microglobulin on the MHC 1 complex?

Answer 7

• stabilizes the complex

- promote release from calnexin

Question 8

MHC 1 binds peptides that are which length?

Answer 8

8-10 amino acids long.

Question 9

which part of the MHC class 1 binds the antigen?

Answer 9

The alpha subunits

Question 10

where is MHC class 1 produced?

Answer 10

In the E.R.

Question 11

Know order of MHC class 1 pathway to surface.

Answer 11

1) (E.R bound) Pre-MHC 1 bound to Calnexin.
2) Beta 2 microglobulin binds MHC 1 displacing Calnexin.
3) MHC 1 binds to calreticulin, ERp57, & Tapasin
4) Proteases degrade intracellular peptides
5) Fragmented peptides passed through TAP into the lumen of ER
6) ERAAP binds peptide fragments in ER lumen, shaves to correct size, and places on MHC 1.
7) MHC releases form all attaching proteins, and exported to cell membrane.

Question 12

where do the peptides come from that are being presented on MHC class 1 molecules?

Answer 12

1) cytosolic proteins. (ex. normal or viral)
2) defective proteins
3) Retrotranslated proteins from ER

Note: dendritic cells can also place endocytosed proteins in cytosol and endocytosed proteins from recycled MHC 1

Question 13

what is cross presentation?

Answer 13

The mechanism used by dendritic cells to load extracellular proteins onto MHC class 1.

Question 14

why is cross presentation critical?

Answer 14

it is necessary for the ability of dendritic cells to activate naive CD 8 T-cells. In order for dendritic cells to do this, they first need to be activated by CD4 T- cells. (this is called licensing)

Question 15

what is “Licensing”?

Answer 15

The activation of dendritic cells by CD 4 T cells is called licensing.

Question 16

How do exogenous proteins get into the cell to become expressed on MHC class 1?

Answer 16

The proteins are phagocytosed, and transported to the cytosol by Sec61 complex. From there they are degraded by a proteosome and loaded onto MHC class 1 through the normal pattern.

Question 17

what makes up the MHC class 2?

Answer 17

alpha and beta chains.

Question 18

which part of the MHC 2 binds the antigen?

Answer 18

both alpha and beta.

Question 19

how long are the chains that MHC 2 binds?

Answer 19

12-20 amino acids.

Question 20

where do you generally find MHC class 1 molecules? what about class 2?

Answer 20

class one= every nucleated cell in the body
class two= on antigen presenting cells (macrophages, B-cells, and dendritic cells)

Question 21

What is the process to get the antigen onto MHC 2?

Answer 21

1) MHC bound to invariant chain in ER lumen.
2) endosome buds off and becomes acidic, causes invariant chain break, clip still blocks active site.
3) Endocytosed antigens are imported and degraded and fuse with MHC 2 endosome.
4) HLA-DM binds to MHC 2 endosome displacing CLIP allowing other peptides to bind.
5) endosome fuses with cell membrane.

Question 22

where do the antigen presenting cells get the peptides that are to be placed on MHC 2?

Answer 22

phagocytosis
macropinocytosis
autophagy

Question 23

which receptor is required for eliminating intracellular pathogens? which is required for activating the adaptive immune response to all pathogens?

Answer 23

1) MHC 1 which activates CD8

2) MHC 2 which activates CD4

Question 24

on which chromosome do you find the MHC locus? how many genes are there?

Answer 24

chromosome 6, and there are 200 genes

Question 25

T/F MHC class 1 genes have higher numbers of alleles because they encode the entire peptide cleft?

Answer 25

true

Question 26

which class of MHC (1 or 2) has higher diversity?

Answer 26

Class 2. Although class 1 has a larger number of alleles, the class 2 molecules undergo random recombination of the alpha and beta genes.

Question 27

what are the 3 classes of type 1 MHC? Type 2?

Answer 27

Type 1 = A,B,C

Type 2 = DP, DQ, DR

Question 28

T/F Class 1 and class 2 MHC are both polymorphic and polygenic?

Answer 28

true.
Polymorphic= having multiple alleles for the same gene.
Polygenic= having multiple genes with the same function.

Question 29

what allows for MHC 1 and 2 to have so much diversity?

Answer 29

different inherited combinations of alleles at the MHC genes. We can have up to 16 different combinations from parents.

Question 30

what is a haplotype? what does it mean when the MHC locus in inherited as a haplotype?

Answer 30

1) Haplotype: the particular combination of MHC alleles on a single chromosome (linked groups of 3)
2) It means that these combinations (haplotype) are inherited as if they were a singe gene.

Question 31

where do you find the majority of diversity of the MHC classes?

Answer 31

in the peptide binding clefts

Question 32

specific haplotypes of MHC class II have been linked to the pathogenesis of what?

Answer 32

autoimmune disorders.

Question 33

T/F If i have a know pathogenic haplotype, I will end up with a disease?

Answer 33

false, the presence of a pathogenic haplotype does not cause the disease, but increases susceptibility.

Question 34

what frequently causes transplant rejection?

Answer 34

peptides from the donor as antigen. Host T cells recognize the MHC from the donor and attack the graft.

Question 35

which type of cell generally tries to reject the new organ transplant?

Answer 35

CD8 T cells because they are looking for the incorrect MHC class 1 which are on every cell.

Question 36

which types of transplants match MHC compatibility?

Answer 36

kidney and bone marrow mainly.

Question 37

What is type 2 bare lymphocyte disease?

Answer 37

when there are defects in the transcription factors needed for MHC II expression. This means that you cant activate any CD4 cells.
These patients have reduced CD4 cells and die by the age of 10 by an infection.

Question 38

what is type 1 bare lymphocyte disease?

Answer 38

when there is a defect in the expression of TAP1, TAP2, or Tapasin.
The patients develop a sensitivity to bacteria and parasites, but usually dies from respiratory insufficiency.

Question 39

how does a superantigen work to kill the host?

Answer 39

it activates both the MHC and the TCR in very large quantities with cytokine release causing it to be overwhelmed. This eventually leads to immune suppression and vulnerability to the pathogen.

Question 40

T/F bacteria, mycoplasms, and viruses can all produce superantigens?

Answer 40

true

Question 41

viruses can block proper function of MHC class 1. why do they usually mess up class 1 and not 2?

Answer 41

because they are intracellular pathogens and they want to live.
They can block TAP, Compete with taposin, or even ubiquinate the MHC complex for distruction.

Question 42

what distroys those cells that do not present with MHC class 1 complexes?

Answer 42

NK cells. This is why they target cancer and viral infected cells. The normal MHC class 1 receptor acts as an inhibitor to the Nk cell when present.