Lecture 11 - TCR Flashcards

1
Q

What are T cell receptors?

A

Membrane-bound Ig-like molecule expressed on T cells

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2
Q

What affinity do TCRs bind with?

A

Low affinity

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3
Q

TCR binding affinity vs antibody

A

TCR - 3-30x10^-6 M binding Antibody - 10^-9 - 10^-12 M binding

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4
Q

TCR structure 1) 2) 3) 4) 5) 6)

A

1) Two chains: alpha and beta chain 2) Each chain made up of a constant region and a variable region 3) Variable region is on top 4) Disulphide link between alpha and beta chains below C region 5) Charged regions in plasma membrane 6) No signalling motifs in cytoplasmic reigon

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5
Q

Is the proteosome a specific immune system protein?

A

No Highly conserved, from bacteria, so not initially required for antigen processing

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6
Q

How does TCR send an effector signal?

A

Recruits CD3, which includes ITAM

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7
Q

What is ITAM?

A

Immunoreceptor Tyrosine-based Activation Motif Involved in TCR and BCR signal transduction

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8
Q

What makes up CD3?

A

Gamma, delta, epsilon, zeta chains

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9
Q

Where is ITAM found?

A

Cytoplasmic region of CD3, Igalpha/Igbeta BCR cytoplasmic region

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10
Q

What is a gamma/delta TCR?

A

Uncommon type of TCR Cells expressing gamma/delta instead of alpha/beta TCR are often CD4-, CD8-. Function not known

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11
Q

Do T cell specificities change during the immune response?

A

No. No equivalent of somatic hypermutation

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12
Q

Which TCR chain has V, D and J regions?

A

Beta

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13
Q

Which TCR region has V and J regions?

A

Alpha

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14
Q

Difference between T cell genomes and other cells

A

In T cell genomes, TCR alpha and beta chain loci have undergone somatic rearrangement In other cells, these are in germline configuraiton

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15
Q

How do T cell alpha and beta chains undergo somatic rearrangement?

A

With heptamer/nonamer RSS, 12/23 rule, V(D)J recombinase complex With allelic exclusion

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16
Q

Which hypervariable region makes most contact with antigen?

A

CDR3

17
Q

What determines TCR specificity?

A

Combinations of Valpha/Jalpha and Vbeta/Dbeta/Jbeta, with N region variability

18
Q

Rough guide to where CDRs bind to MHC/antigen complex

A
19
Q

Is TCR recombination random?

A

Not completely In beta recombination, D and J regions are linked

20
Q

Do all residues of peptide antigen make contact with TCR?

A

No

21
Q

Does V have to make contact with antigen?

A

No. V, D or J can make contact with antigen

22
Q

What is a superantigen?

A

An antigen that can stimulate an inordinately large number of T cells without procesing

23
Q

Example of a superantigen

A

Toxic shock syndrome toxin

24
Q

Where does toxic shock syndrome toxin bind?

A

Binds directly to Vbeta10 regardless of D or J region. Will interact with MHC, without TCR making contact with MHC

25
Q

Number of TCR which can bind a MHC/antigen complex

A

Well under 0.01%

26
Q

Number of TCR stimulated by a superantigen

A

Between 1-10% of TCR, depending on which Vbeta is stimulated by superantigen

27
Q

What must a T cell do to be released into the periphery?

A

Recognise a self MHC/foreign antigen complex Not bind too tightly to a self MHC

28
Q

What is an allogenic MHC? 1) 2) 3)

A

1) A foreign MHC molecule (EG: from a graft) that is recognised by T cells. 2) Same shape as a self MHC/foreign antigen complex. 3) Attacked by T cells as such

29
Q

How can a TCR recognise an allogenic MHC? 1) 2)

A

1) Allogenic MHC same shape as a self MHC/foreign antigen complex 2) Allogenic MHC binds a peptide, allogenic MHC/peptide complex same shape as a self MHC/foreign antigen complex

30
Q
A
31
Q
A
32
Q

TCR alpha locus structure

A

Va1 | VaN | VaJ | Ca

33
Q

TCR beta locus structure

A

Vbeta1 | VbetaN | VbetaD1 | VbetaJN | C beta | VbetaD2 | VbetaJN | Cbeta