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Immunology > T cell Diversity > Flashcards

T cell Diversity Flashcards

1
Q

What are the two phases in an immune response graph?

A

Expansion phase followed by contraction phase

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2
Q

What can T cells TCR be made up of?

A

Alpha and beta chains
Gamma and delta chains

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3
Q

What TCR do CD4 & CD8 have?

A

Alpha-beta chains

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4
Q

What is an iNKT?

A

Invariant natural killer T

Expresses an invariant aβ TCR and a number of cell surface molecules in common with natural NK cells

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5
Q

What are MAIT cells?

A

Mucosal-associated invariant T cells

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5
Q

What MHC do MAIT bind to?

A

MHC Class I restricted

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6
Q

What initiates TCR arrangement?

A

Pre-cursor committing to T-cell lineage

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7
Q

What type of selection do T cell go through?

A

Positive and negative selection

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8
Q

What happens when T cell mature?

A

Leave thymus to go to secondary lymphoid organ where they can encounter antigen

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9
Q

Before T cell encounter an antigen what are they considered?

A

Immunologically naive

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10
Q

How do T cell precursors commit to T cell lineage?

A

Notch signalling helps determine whether they become CD4+ helper T cells or CD8+ cytotoxic T cells

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11
Q

How many constant regions are in alpha and beta chains?

A

V and J segments with 1 constant region
V,D and J segments with 2 constant regions

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12
Q

What type of dimerization do TCR have?

A

Heterodimers between alpha and beta chain

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13
Q

What does RSS stand for?

A

Recombination signal sequence

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14
Q

What is the V segment recombination signal sequence?

A

Heptamer
23 base pair spacer
Nonamer

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15
Q

What is the J segment recombination signal sequence?

A

Heptamer
12 base pair spacer
Nonamer

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16
Q

What would happen without the 12/23 rule when there is a forward and reverse gene present?

A

V genes can recombine together because one is in the forward direction and the other is in the reverse direction

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17
Q

What happens when forward-oriented V gene segment recombines with downstream gene segment?

A

Alignment of the two RSS regions loop out intervening DNA
This loop is excised from chromosome = deleted signal joint
Giving a recombination

18
Q

What happens when reverse-oriented V gene segment recombines with downstream gene segment?

A

Alignment of RSS regions forms the intervening DNA into coiled configuration
Coiled region is retained in the chromosome
Inverted orientation of recombination???

19
Q

What happens when 12/23 rule is present?

A

RAG1/2 recognize the 12/23 recombinatorial signal sequence
Synapsis of two RSSs = covalently closing DNA hairpin

20
Q

What creates junctional diversity?

A

TdT adds random nucleotide

21
Q

What is the mechanism of generating junctional diversity?

A

RSS brought together
RAG complex generates DNA hairpin at coding ends
Artemis: DNA-PK complex opens DNA hairpins = generating palindromic P-nts
Tdt adds random nucleotides
Pairing of strands
Unpaired nucleotides = removed by exonuclease
Gaps are filled by DNA synthesis and ligation = form coding joint

22
Q

What is the role of sequential TCR rearrangement?

A

Repeated rearrangements can rescue non-productive VJ alpha joins

23
Q

What does CDR3 of both alpha and beta chain recognize?

A

Antigen-peptide recognition

24
Q

What do CDR1/2 of alpha chain recognize?

A

N terminus of MHC

25
Q

What do CDR1/2 of beta chain recognize?

A

C terminus of MHC

26
Q

Describe CDR1/2 genes

A

V-encoded and germline encoded

27
Q

Describe CDR3 genes

A

J-encoded in alpha
D-J encoded in beta
Both = hypervariable because of nucleotide additions via TdT

28
Q

Difference in TCR gamma-delta recombination?

A

A lot less diverse
Delta chain genes sit in alpha chain

29
Q

If there is too much diversity of TCR, what are the potential issues?

A

TCR do not recognize (self) MHC
TCR do not recognize self antigens

30
Q

What happens in the medulla region of thymus?

A

Thymocytes mature and cellular degradation occurs

31
Q

What happens in the cortex region of thymus?

A

Immature thymocytes start there = bone marrow origin

32
Q

When is the thymus fully developed in humans?

A

At birth

33
Q

What is thymic involution?

A

When thymus begins to shrink after puberty?

34
Q

When is T cell production highest?

A

Greatest before puberty

35
Q

Order of T cell development

A

Hematopoietic stem cells
Common lymphoid progenitor (CLP)
PreT cell = thymus
CD4+ or CD8+ = peipheral blood

36
Q

What happens in the first step of thymocyte maturation?

A

CLP enters thymus and receives signals from Notch1 receptor
Notch1R causes upregulation of TFs = TCF1 and GATA3
These TF commit CLP to the T cell lineage
CLP develops and upregulates the gene RAG1

37
Q

What happens in DN2 of thymocyte maturation?

A

RAG1 gene recognizes 12/23 rule and cleaves
Recombination happens in the beta locus
Once beta chain is recombined = can be successful or non-productive

38
Q

What happens in DN3 of thymocyte maturation?

A

If recombination is non-productive ou will not get pairing with pTa = no pre-TCR made

If successul = can pair with pTa so you can form pre-TCR

39
Q

What is the point of the pre-T cell alpha?

A

Checkpoint to see if there is successful beta chain recombination

40
Q

When is RAG1 downregulated?

A

Only when there is a positive pre-TCR signal
This is because recombination is no longer needed

41
Q

What happens when there is a good pre-TCR alpha?

A

RAG1 will be downregulated
Cell will receive signal and start to proliferate

42
Q

What is the DN4 part of thymocyte maturation?

A

After proliferation RAG1/2 is expressed again
This causes alpha chain rearrangement

Immunology (8 decks)

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