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Molecular Basis Of Disease/ Microbiology And Immunology > T Cell Development: Generation Of Receptor Repertoire Diversity > Flashcards

T Cell Development: Generation Of Receptor Repertoire Diversity Flashcards

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Biology 101 flashcards
1
Q

What are the events in lymphocyte development?

A

Commitment
Proliferation
Selection
Differentiation into distinct functional effector sub populations

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2
Q

What are the key factors in lymphocyte development?

A

Stem cell factors (c-KIT)
Cytokines (IL-7, IL-3)
Tissue specific signals (notch and thymic stromal cells)

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3
Q

What do multipotent HSCs give rise to?

A

B and T cell lineages

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4
Q

What happens in the pro-lymphocyte stage of T cell maturation?

A

Growth factor mediated commitment, proliferation and initiation of antigen receptor gene arrangement all happen

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5
Q

What happens in the prelymphocyte stage of T cell maturation?

A

Selection of cells that express pre-antigen receptors

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6
Q

What does the thymus contain?

A

A dense network of stromal (epithelial) cells and lymphocytes

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7
Q

Where do T cell progenitors develop?

A

In the bone marrow and migrate to the thymus

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8
Q

What happens to T cell progenitors in the thymus?

A

Positive and negative selection (selects for non-self recognising cells)

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9
Q

What causes the T cells to mature?

A

Notch signals sent from the thymic stroma

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10
Q

Where do mature T cells migrate to?

A

Peripheral lymphoid organs

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11
Q

Where do activated T cells migrate to?

A

The site of infection

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12
Q

How do notch signals cause maturation and proliferation of T cells?

A
  • > induction of GATA3
  • > commitment to the T cell lineage
  • > intense proliferation
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13
Q

How long after the arrival of precursors in the thymus do the progenitors commit to the T cell lineage?

A

1 week

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14
Q

What do T cell progenitors express when they first arrive in the thymus?

A

CD2 and Thy1

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15
Q

Why are early developing T cells called double negatives?

A

No CD4 or CD8

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16
Q

What happens in the double negative stage?

A

Developing T cells rearrange the TCR locus

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17
Q

What happens to the T cell after the double negative stage?

A

Go double positive
Resting stage
Split into single positives before going into the periphery

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18
Q

What do T cells express if they’re successfully rearranged and selected?

A

High levels of TCR

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19
Q

What is a TCR made up of?

A

A heterodimer consisting of two transmembrane polypeptide chains covalently linked to each other by disulphide bonds

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20
Q

What are the two types of TCR?

A

Alpha-beta and gamma-delta

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21
Q

What does each TCR chain have?

A

One Ig-like N terminal variable domain and one Ig-like constant domain
A hydrophobic transmembrane region and a short signalling cytoplasmic region

22
Q

What does CDR stand for?

A

Complementary determining regions

23
Q

What forms the peptide-MHC binding site?

A

3 CDRs of the alpha chain and 3 of the beta chain

24
Q

What brings the chains together in the C regions?

A

Cysteine residues

25
Q

What are the features of antigens recognised by T cells?

A

Linear peptides
Cell associated antigens
CD4+ recognise cells from the extracellular pool
CD8+ recognise cells from the cytosolic pool

26
Q

What do MHC-I molecules present?

A

Peptide antigens derived from pathogens that replicate inside the cell (viruses)

27
Q

What do MHC-II molecules present?

A

Peptides from pathogens and antigens that are present outside the cell and taken up by endocytotic vesicles of phagocytic cells

28
Q

What is the structure of MHC class II molecules?

A

Extracellular peptide binding cleft
Ig-like domain
Cytoplasmic tail
Conserved CD4 binding site

29
Q

What are some features of MHCs?

A

Highly polymorphic and polygenic

30
Q

How many peptides can one MHC bind at a time?

A

One

31
Q

What do different peptides that bind to the same MHC share?

A

Structural features that promote binding

32
Q

How many MHC-peptide complexes are needed to activate a T cell?

A

Very small number

33
Q

Do MHC-I or II bind the longer peptides?

A

MHC-II

34
Q

Where are MHC-Is expressed?

A

On all cells apart from erythrocytes

35
Q

Where are MHC-II molecules expressed?

A

APCs

36
Q

What is the pathway for antigen processing and presentation on a MHC-II?

A

Extracellular protein uptake
Processing of proteins in vesicles
Biosynthesis and transport of class II MHC molecules to endosomes in the golgi
Association of processed peptides with MHC-II molecules in vesicles
Expression of peptide-MHC complex on cell surface

37
Q

How are TCRs rearranged?

A

First a D fragment is joined with a J fragment and then the V fragment is joined to the DJ fragment

38
Q

What are some properties of the TCR?

A

Only one TCR form is expressed on each T cell
They clone to get daughter cells
TCR only has one antigen binding site

39
Q

Are there D regions on alpha TCRs?

A

No

40
Q

How are the T cell receptor gene segments arranged?

A

In a similar pattern to the Ig gene segments and are rearranged by the same enzymes

41
Q

Where do the TCRs concentrate their diversity?

A

The third hypervariable region CDR3

42
Q

What mediates the recombination events in the biosynthesis of TCR?

A

RAG 1 and 2 gene

43
Q

What happens before biosynthesis of TCR?

A

Beta chain rearrangement

44
Q

Why would TCR alpha be rearranged many times?

A

Until a productive rearrangement is achieved

45
Q

What is junctional diversity?

A

Addition or removal of nucleotides creating new sequences at junctions

46
Q

What is junctional diversity mediated by?

A

TdT - terminal deoxynucleotidyl transferase

47
Q

Where (physically) do gene rearrangement checkpoints occur?

A

Within particular regions of the thymus

48
Q

What is allelic exclusion?

A

Signalling through the pre-TCR supresses expression of the RAG genes, so no more rearrangement at this stage

49
Q

What does allelic exclusion ensure?

A

Only one beta chain is expressed

50
Q

What happens when a successful pre-TCR rearrangement is formed?

A

Further beta chain rearrangement is halted
Induce expression of CD4 and CD8
Initiates alpha chain rearrangement

Molecular Basis Of Disease/ Microbiology And Immunology (57 decks)

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