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Immunology > T cell receptor, antigen recognition > Flashcards

T cell receptor, antigen recognition Flashcards

1
Q

How do T cells differ from B cells? Development.

Location?

A

Thymus (T cell)
- positive and negative selection happen here

Bone marrow (B cells)
- negative selection
- BUT for positive selection they go to secondary lymphoid organs

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2
Q

Receptor

B vs T cells

A

similar mechanism but different structure

  • both derived from gene rearrangement
  • B cell has four chains
  • T cell has two chains
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3
Q

Isotype switching?
Affinity maturation?

T vs B cells

A

Isotype switching
- T cells do not undergo isotype switching or affinity maturation.

The constant region of the T cell recepor does not have specific functions, like the Fc (constant region of heavy chain) on B cell receptors

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4
Q

How do B and T cells recognize antigens

A

T cells require MHC

B cell receptors recognize antigens directly (do not need MHC) - they can simply bind to native antigens

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5
Q

Function of T vs B cells

A

T cells - either kill infected host cells or make cytokines

B cells - make antibodies

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6
Q

Beta chain - somatic recombination

A

VDJ

like the heavy chain of B cell receptor

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7
Q

alpha chain - somatic recombination

A

VJ

like the light chain of B cell receptors

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8
Q

VDJ segment encode

A

antigen binding site on the beta chain of T cell receptor

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9
Q

VJ segment encode

A

antigen binding site on the alpha chain of the T cell receptor

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10
Q

Where is there more varible segments (V) in T cell receptors?

A

Alpha

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11
Q

D segments in immunoglobin and T cell receptors

A

Only in Heavy chain (B cell)
- has more than in T cell receptors

Only in beta (T cell )

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12
Q

Joining segments

A

About equal in B cells between H and lambda/kappa

Very numerous in the alpha chain of T cell receptor

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13
Q

Junctional diversity

A

Much higher in T cell receptors, compared to in B cell receptors

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14
Q

Which type of receptor has more total diversity

A

Significanly higher in T cells receptors.
5 orders of magnitude difference

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15
Q

Two classes of T cell receptors

A
  1. Alpha + Beta = most common
  2. Gamma + delta

This decision is made during rearrangement

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16
Q

Alpha + beta T cell receptor

A
  • Most common / majority of Conventional T cells
  • Recognize MHC/peptide
  • High degree of receptor diversity
  • Cells abundant in all secondary lymphoid tissues
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17
Q

Both types of T cell receptors:

A
  • Always transmembrane
  • Short cytoplasmic tails
  • Constant region - does not participate in antigen binding
  • Variable regions - antigen binding site
    1. variable regions are made up of two chains
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18
Q

Gamma / delta
T cell receptor

A
  • Smaller subset of T cells
  • Recognition specificity not fully clear, MHC class Ib
  • Lower degree of receptor diversity
  • Cells abundant in gut mucosa
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19
Q

Types of alpha/beta T cells receptors

A

CD4+ T helper cells
CD8+ Cytolytic T cells

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20
Q

CD4+ T helper cells

A
  • Upon activation, produce cytokines to “help” other cells clear infection
  • Recognize MHC class II via CD4 interaction
  • Antigens presented to these T cells tend to be from extracellular sources
  • Depending on the cytokines produced, these cells can be further sub-divided
21
Q

CD8+ Cytolytic T cells (CTL)

A
  • Upon activation, kill target cells through several mechanisms
  • Recognize MHC class I via CD8 interaction
  • Antigens presented to these cells end to ocme from cytoplasmic sources
22
Q

CD4 structure

A

Monomeric protein consisting of D1-D4

23
Q

CD8 structure

A

Dimer

consiting of alpha and beta

24
Q

CD8 binds the _ domain of _

A

Alpha3

MHC Class I

25
Q

CD4 binds the _ domain of _

A

Beta2

MHC Class II

26
Q

TCR complex

A

The TCR needs the help of CD3 signaling complex to transmit signals for activation

CD3 (signaling adapting molecule) also required for cell surface expression.

CD3 initiates a signaling transduction cascade

27
Q

CD3 chains

A

Conists of 6 chains

  • 2 epsilon
  • 2 zeta
  • 1 gamma
  • 1 delta
28
Q

CD3 complex

A

accompanies the actual T cell receptor (alpha and beta chain), but does not participate in antigen binding

Not part of the T cell receptor, although it helps with the signaling for that receptor

29
Q

Steps in T cell receptor formation

A
  1. Beta, gamma and delta chains attempt rearrangement simultaneously. Order of gene segment selection is similar to B cells
    - if beta is succesful, then it is tested with the pre-TCR (beta+pTalpha) - surrogate light chain
    - if gamma and delta are both successful, then rearrangement is complete and the cell will be a gamma/delta.
  2. Alpha, gamma, delta chains attempt rearrangement simultaneously
    - if alpha is succesful, then it is combined with beta and selection can begin
    - If gamma and delta are both succesful, then rearrangement is complete and the cells will be a gamma/delta
30
Q

surrogate alpha chain in T cell receptor

A

Pre - TCR

(beta+pTalpha)

tests if the beta chain is able to pair with alpha.

31
Q

A common double negative T cell receptor progenitor gives rise to A;B and Y;D T cells

A
  1. uncomitted proginitor (CD34) and travel from BM to thymus
  2. Committed double negative T cell progeniator (express CD2)
  3. Beta, gamma and delta rearrangement
    - if beta is succesful, the beta chain will be tested with the preTcell receptor surrogate chain
    - if succesful, rearrangement on alpha, delta and gamma occur. If gamma and delta rearranges before alpha, the cell becomes a gamma/delta T cells
  • If the gamma delta rearrangement happened before beta, the cell becomes a y;d cell
32
Q

Expression of CD4 and CD8 during rearrangement

A

When cells enter the thymus, they express neither CD4 or CD8. (making them a double negative cell)

When they have succesfully come to the preTcell receptor stage (not yet committed), they will upregulate both CD4 and CD8 (making them double positive).

When the cell has comitted to be a CD4 or CD8, they are (single positive, because they only express either CD4 or CD8)

After they have gone through the entire selection process, they become a single positive cell.

33
Q

if the gamma/delta rearrangement is succesful

A

the gamma:delta cell matures, leaves the thymus and migrates to peripheral tissue

NO pre-TCR stage on gamma;delta cells

34
Q

If the beta chain rearrangement is succesful

A

Pre TCR testing

then, the pre-T cell resumes rearrangement of alpha, gamma and delta.

35
Q

Why do y;d cells not go through a stage where they express a Pre-TCR?

A

because both receptor are rearranged at the same time.
No time/room for a pre T cell receptor test.

36
Q

Pre-TCR serves a parallel purpose to the Pre-BCR

A
  • Test the ability of a rearranged B chain to form a complex with the pre T-alpha chain
  • Stops rearrangement at the other beta locus (second chromosome) - allelic exclusion
37
Q

Pre T cell receptor
vs
T cell receptor

A

pTalpha is present in the Pre T cell receptor, whereas in a T cell receptor alpha has taken pTalpha’s place.

pTalpha forms with beta to make sure that the beta is fully formed and ready to pair with alpha.

38
Q

Productive rearrangement of the beta locus

A

only two attempts can be made to achieve a productive rearrangement

Each chromosome **has two chances to generate a rearrangemnt of the beta chain locus. **

total = four attempts to make a beta chain

the alpha chain locus can sustain many attempts at a functional rearrangement

39
Q

important implication for A:B vs Y:D TCR rearrangement

A

the delta gene segments are situated within the alpha gene locus, so rearrangement of the alpha chain results in deletion of the delta loci, so no chance to make a Y:D TCR.

40
Q

delta regions

A

VDJ

41
Q

gamma regions

A

VJ

42
Q

rearrangement of an alpha chain gene results in

A

the elimination of delta chain locus.

43
Q

RAG expression

A

reflects the timing of rearrangement of the beta and alpha chains.

Rearrangement:
- V-J beta (first checkpoint)
- V-DJ beta (first checkpoint)
- V-J alpha (second checkpoint)

44
Q

CD4, CD8 function

A

Co-receptor

After the Pre-T cell receptor has been sucessfully tested.

45
Q

RAG1-2 function

A

Lymphoid specific recombinase

Rearrangment of b,y,d
Rearrangment of a,y,d

46
Q

when are CD4 and CD8 expressed

A

When T cells begin rearrangement they are CD4 and CD8 double negative

When the Pre-TCR is tested and proven to be succesful, CD4 and CD8 will be upregulated (double positive)

After selection is complete, and the T cell is ready to enter periphery, only CD4 or CD8 is expressed

47
Q

CD8 T cell + virus infected host cell

A

killing of the virus infected cell

shuts off viral infection

48
Q

CD4 T cell help + macrophage

A

Macrophage may express MHCII complexes which are recognized by CD4-T cell and the CD4-T cell secretes cytokines such as IFNy which activates the macrophage.

The macrophage is now able to kill bacteria and secrete cytokines to increase inflammation

49
Q

CD4 T cells + B cell

A

Important for B cell activation

CD40/CD40L interaction + cytokines.

These signals instruct the B cells to perform isotype switching and differntiation.

This cell may now become a B cell that secretes antibodies/

Immunology (18 decks)

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