MHC, Antigen Presentation & T - cell activation

Question 1

Organization & Inheritance of MHC

What can Class 1 MHC be found?
And which cell are they presenting antigen to?

Answer 1

Nearly all nucleated cells

Tc cells

Question 2

Organization & Inheritance of MHC

Where can Class 2 MHC be found?
And what cells are they presenting antigen to?

Answer 2

APC ( Antigen - presenting cells )
e.g. Macrophages, dendritic cells & B cells

Th cells

Question 3

What is MHC referred to in humans and mice?

Answer 3

Human
-> HLA complex ( human leukocyte antigen )

Mice
-> H-2 complex

Question 4

Organization & Inheritance of MHC

Can a mouse with MHC haplotype of b/b donate skin to its k/k parent?
Can the same mouse donate skin to its b/b parent?

Can a mouse with MHC haplotype of b/k donate skin to its k/k, b/b parents?

Answer 4

No
Yes

No

Question 5

MHC molecules / distribution & interaction with peptide

Which of the following antigen will interacts with MHC?

Peptide
Polypeptide
Protein
Glycoprotein

Answer 5

Peptide

Question 6

MHC molecules / distribution & interaction with peptide

What are the 2 components that make up MHC - 1 distal domain?

Answer 6

Alpha 1 & Alpha 2

Question 7

MHC molecules / distribution & interaction with peptide

What are the 2 components that make up MHC - 1 proximal domains?

Answer 7

alpha 3 & beta 2 - microglobulin

Question 8

MHC molecules / distribution & interaction with peptide

Is alpha 1, 2 ,3 part of the same chain?

Answer 8

Yes

Question 9

What is the meaning of polymorphic?
Which parts of MHC - 1 are polymorphic?

Answer 9

Polymorphic :
Diverse within a population since your parents determines your allele
It adds diversity to a population

Alpha chain is polymorphic

Question 10

MHC molecules / distribution & interaction with peptide

Where is the peptide - binding cleft located in MHC 1?
Peptide - binding cleft will bind to peptide with how many a.a.?

Answer 10

Between alpha 1 & alpha 2
8 - 10 a.a.

Question 11

MHC molecules / distribution & interaction with peptide

Is beta 2 - microglobulin encoded by a MHC gene ?

Answer 11

Nope

Question 12

MHC molecules / distribution & interaction with peptide

What is the 2 components that make up the MHC - 2 distal domains?

Answer 12

Alpha 1 & Beta 1

Question 13

MHC molecules / distribution & interaction with peptide

What is the 2 components that make up the MHC - 2 proximal parts?

Answer 13

Alpha 2 & Beta 2

Question 14

MHC molecules / distribution & interaction with peptide

Where is the peptide - binding site located in MHC - 2?
Peptide - binding site will bind to peptide with how many a.a.?

Answer 14

Between alpha 1 & beta 1
13 - 18 a.a.

Question 15

MHC molecules / distribution & interaction with peptide

Which superfamily is MHC - 1 / 2 classified in?

Answer 15

Ig superfamily

Question 16

MHC molecules / distribution & interaction with peptide

Which part of MHC - 2 is polymorphic?

Answer 16

alpha 1 & beta 1

Question 17

MHC molecules / distribution & interaction with peptide

Why is there no genetic rearrangement in production of MHC compared to antibodies production in B cell?

Answer 17

Polymorphic

• MHC varies between individual
  -> But one individual produces only one kind of MHC

Question 18

MHC molecules / distribution & interaction with peptide

How do you calculate the MHC - 1 diversity for an individual?

Answer 18

Since MHC - 1 is solely dependent on alpha chain

Mother MHC - 1 alleles + Father MHC - 1 alleles

E.g.
Mother MHC - 1 alleles : K^k / D^k / L^k
Father MHC - 1 alleles : K^d / D^d / L^d

Kid : Mother + Father = K^k / D^k / L^k / K^d / D^d / L^d

Question 19

MHC molecules / distribution & interaction with peptide

How do you calculate MHC - 2 diversity for an individual?

Answer 19

Since MHC - 2 diversity depends on an alpha chain & a beta chain

( Mother MHC - 2 alleles + Father MHC - 2 alleles ) x2

E.g.
Mother MHC - 2 alleles : IA a^k b^k / IE a^k b^k
Father MHC - 2 alleles : IA a^d b^d / IE a^k b^d

Kid : ( Mother + Father ) x2
-> IA a^k b^k / IA a^d b^d / IA a^k b^d / IA a^d b^k
-> IE a^k b^k / IE a^d b^d / IE a^k b^d / IE a^d b^k

Question 20

MHC molecules / distribution & interaction with peptide

Which cell has the highest level of MHC - 1?

Answer 20

Lymphocytes

Question 21

MHC molecules / distribution & interaction with peptide

Which is anchor residues and the purpose of it?
Which numbers of a.a. are anchor residues?
Which number of a.a. has the highest affinity?

Answer 21

a.a. that are complementary with binding cleft
-> creates a bulge
that looks like this -../.

Anchor residues : 2, 3 ,9
9 ( nomameric peptides ) bind to MHC-1 100-1000 fold higher affinity

Question 22

MHC molecules / distribution & interaction with peptide

Where does MHC - 1 molecules bind peptides come from?

Answer 22

Endogenous intracellular protein
-> digest in cytosol

Question 23

MHC molecules / distribution & interaction with peptide

Where does MHC - 2 molecules bind peptide come from?

Answer 23

Exogenous protein
-> Degraded within endocytic processing pathway

Question 24

MHC molecules / distribution & interaction with peptide

Does both MHC - 1 & 2 bind peptide have anchor residues?

Answer 24

Only MHC - 1 bind peptide anchor residues

Question 25

Self - MHC restriction of T cell Can Tc cells kill target cells with different haplotype of MHC - 1?

Answer 25

NOPE

Question 26

Self - MHC restriction of T cell What does“ Self MHC, Foreign peptide “ mean?

Answer 26

TCR will only bind with cells with self MHC TCR will only bind with non self peptide

Question 27

Antigen - presenting cells & presentation pathways What is antigen processing & antigen presentation?

Answer 27

Antigen processing : -> Metabolic process - -> Degrade protein antigen into peptides Antigen presentation : -> Peptide - MHC complexes - -> Transported to membrane

Question 28

Antigen - presenting cells & presentation pathways Which of the following is the most effective APCs? Dendritic cells Macrophages B cells

Answer 28

Dendritic cells

Question 29

Antigen - presenting cells & presentation pathways Which of the following must be activated before they become APC? How are they activated and what do they express after they are activated? Dendritic cells Macrophages B cells

Answer 29

Macrophages -> Phagocytosis - -> MHC - 2 - -> B7 B cells -> Ag - mIg activation - -> B7

Question 30

Antigen - presenting cells & presentation pathways What are the 4 steps in MHC - 1 endogenous pathway?

Answer 30

Degradation of endogenous antigen by proteasome Peptide -> RER via TAP channel Binding of peptide & MHC - 1 Peptide - MHC complex [ RER -> Golgi -> Membrane ]

Question 31

Antigen - presenting cells & presentation pathways What are the 6 steps of MHC - 2 exogenous pathway?

Answer 31

Invariant chain binds onto MHC - 2 alpha & beta -> blocks binding of endogenous antigen MHC complex -> Golgi -> Endocytic pathway compartments Degradation of Invariant chain -> leaving CLIP fragment on MHC complex Exogenous antigen is degraded -> Endocytic pathway compartments HLA-DM exchanges CLIP for antigenic peptide Peptide - MHC complex -> membrane

Question 32

Antigen - presenting cells & presentation pathways What molecules presents non protein antigens ( e.g. glycolipid )?

Answer 32

CD1

Question 33

T - cell receptor complex : structure & role What molecule is responsible for signal transduction and membrane expression of TCR?

Answer 33

CD3

Question 34

T - cell receptor complex : structure & role What are 2 molecules that recognize peptide - MHC complex and are responsible for signal transduction?

Answer 34

CD4 & CD8

Question 35

T - cell receptor complex : structure & role Which cell has CD4 & which cell has CD8?

Answer 35

CD4 : Th cell CD8 : Tc cell

Question 36

T - cell receptor complex : structure & role What does CD4 bind to & what does CD8 bind to?

Answer 36

CD4 : MHC - 2 CD8 : MHC - 1

Question 37

T - cell receptor complex : structure & role Are all TCR made up of alpha& beta chain?

Answer 37

Nope

Question 38

T - cell receptor complex : structure & role What are TCR made up of if not alpha & beta?

Answer 38

gamma & delta

Question 39

T - cell receptor complex : structure & role What does gamma delta T cells TCR bind to?

Answer 39

Microbial phospholipid

Question 40

T - cell receptor complex : structure & role What molecule is used to present antigen captured by gamma delta T cell?

Answer 40

CD1

Question 41

T - cell receptor complex : structure & role Are gamma delta T cell related to innate immune system?

Answer 41

Yes

Question 42

T - cell receptor complex : structure & role What does gamma delta T cell secrete to recruit alpha beta T cell to the site of invasion?

Answer 42

Cytokines

Question 43

T cell receptor : organization & expression In mouse, how many chromosomes are responsible for alpha, delta, beta & gamma chain DNA?

Answer 43

3 in total -> 14 alpha & delta -> 6 beta -> 13 gamma

Question 44

T cell receptor : organization & expression In mouse, do both TCR alpha chain & delta chain DNA contain V D J ?

Answer 44

Nope -> Only delta chain DNA contain VDJ

Question 45

T cell receptor : organization & expression In mouse, what happens in alpha delta DNA so alpha beta T cell can be produced?

Answer 45

deletion of delta chain in alpha delta DNA

Question 46

T cell receptor : organization & expression In mouse, which of the following has VJ DNA? alpha chain DNA delta chain DNA beta chain DNA gamma chain DNA

Answer 46

alpha chain gamma chain

Question 47

T cell receptor : organization & expression What is the 5 mechanisms for generating diversity in TCR genes? ( Tips : 4 of them are in BCR diversity too )

Answer 47

V(D)J recombination ** Alternative joining P - addition ** N - addition ** Junctional flexibility **

Question 48

T cell receptor : organization & expression What is alternate joining?

Answer 48

It only occurs in D gene segments -> Since D genes have One turn RSS on one side and Two turn RSS on another -> They can join together to increase diversity -> While joining 3 things can happen to further increase diversity - -> P - addition - -> N - addition - -> junctional flexibility

Question 49

T cell receptor : organization & expression Alternative joining can happen on which of the following genes? Alpha Delta Beta Gamma

Answer 49

Delta Beta

Question 50

T cell receptor : organization & expression How many CDRs are there in TCR? And what are they called?

Answer 50

3 CDR1, CDR2, CDR3

Question 51

T cell receptor : organization & expression Which CDRs in TCR has the most diverse region for antigen recognition? and why?

Answer 51

CDR3 > CDR1 & CDR2 CDR1 & CDR2 are located within V segment CDR3 is located between the V, (D) & J where many of the diversity mechanisms were applied

Question 52

T cell receptor : organization & expression What are the 2 reasons why T cell doesn’t generate a self - reactive response?

Answer 52

T cells who react with self - antigen - MHC are eliminated in thymus T cells don’t undergo somatic hypermutation -> T cells specificity don’t change after thymic selection

Question 53

T cell selection, activation & differentiation What is the name of the two thymic selection? What do they do?

Answer 53

Positive selection -> Thymocytes who bind to self - MHC molecules survives - -> Thymocytes who don’t have the capability of binding dies Negative selection -> Thymocytes that don’t react strongly to self antigen / self - MHC molecules survives -> Thymocytes that binds strongly to self antigen / self - MHC molecules dies

Question 54

T cell selection, activation & differentiation What are the estimated percentage of thymocytes survives & mature?

Answer 54

2%

Question 55

T cell selection, activation & differentiation What are the central event in generation of both humoral and cell mediated immune responses?

Answer 55

Activatation Clonal expansion

Question 56

T cell selection, activation & differentiation What does CD3 in TCR - CD3 complex do?

Answer 56

It helps stabilize TCR when TCR binds to antigen MHC complex & is responsible for signal transmission

Question 57

T cell selection, activation & differentiation What is the 2 signals required to fully activate T cells?

Answer 57

Ag - mIg ( TCR - CD3 complex ) CD28 - B7 -> Can be suppressed by CTLA - 4 ( Cytotoxic T - Lymphocyte Associated Protein 4 ) on activated T cell

Question 58

T cell selection, activation & differentiation which signal determines clonal anergy or clonal expansion?

Answer 58

Signal 2 -> CD28 - B7

Question 59

T cell selection, activation & differentiation Can signal 2 be activated by external help? (e.g. -> Another APC reaching out with B7

Answer 59

Yes

Question 60

T cell selection, activation & differentiation What are the 3 signal transduction products upon Th cell activation? And when are they expressed? ( Tips : genes )

Answer 60

Immediate genes -> Within 30 mins Early genes -> 1-2 hours Late genes -> After 2 days