Lecture 11 - TCR Flashcards Preview

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Flashcards in Lecture 11 - TCR Deck (33):
1

What are T cell receptors?

Membrane-bound Ig-like molecule expressed on T cells

2

What affinity do TCRs bind with?

Low affinity

3

TCR binding affinity vs antibody

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

4

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

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

5

Is the proteosome a specific immune system protein?

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

6

How does TCR send an effector signal?

Recruits CD3, which includes ITAM

7

What is ITAM?

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

8

What makes up CD3?

Gamma, delta, epsilon, zeta chains

9

Where is ITAM found?

Cytoplasmic region of CD3, Igalpha/Igbeta BCR cytoplasmic region

10

What is a gamma/delta TCR?

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

11

Do T cell specificities change during the immune response?

No. No equivalent of somatic hypermutation

12

Which TCR chain has V, D and J regions?

Beta

13

Which TCR region has V and J regions?

Alpha

14

Difference between T cell genomes and other cells

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

15

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

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

16

Which hypervariable region makes most contact with antigen?

CDR3

17

What determines TCR specificity?

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

18

Rough guide to where CDRs bind to MHC/antigen complex

19

Is TCR recombination random?

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

20

Do all residues of peptide antigen make contact with TCR?

No

21

Does V have to make contact with antigen?

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

22

What is a superantigen?

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

23

Example of a superantigen

Toxic shock syndrome toxin

24

Where does toxic shock syndrome toxin bind?

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

25

Number of TCR which can bind a MHC/antigen complex

Well under 0.01%

26

Number of TCR stimulated by a superantigen

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

27

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

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

28

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

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

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

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

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32

TCR alpha locus structure

Va1 | VaN | VaJ | Ca

33

TCR beta locus structure

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