What are T cell receptors?
Membrane-bound Ig-like molecule expressed on T cells
What affinity do TCRs bind with?
TCR binding affinity vs antibody
TCR - 3-30x10^-6 M binding Antibody - 10^-9 - 10^-12 M binding
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
Is the proteosome a specific immune system protein?
No Highly conserved, from bacteria, so not initially required for antigen processing
How does TCR send an effector signal?
Recruits CD3, which includes ITAM
What is ITAM?
Immunoreceptor Tyrosine-based Activation Motif Involved in TCR and BCR signal transduction
What makes up CD3?
Gamma, delta, epsilon, zeta chains
Where is ITAM found?
Cytoplasmic region of CD3, Igalpha/Igbeta BCR cytoplasmic region
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
Do T cell specificities change during the immune response?
No. No equivalent of somatic hypermutation
Which TCR chain has V, D and J regions?
Which TCR region has V and J regions?
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
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
Which hypervariable region makes most contact with antigen?
What determines TCR specificity?
Combinations of Valpha/Jalpha and Vbeta/Dbeta/Jbeta, with N region variability
Rough guide to where CDRs bind to MHC/antigen complex
Is TCR recombination random?
Not completely In beta recombination, D and J regions are linked
Do all residues of peptide antigen make contact with TCR?
Does V have to make contact with antigen?
No. V, D or J can make contact with antigen
What is a superantigen?
An antigen that can stimulate an inordinately large number of T cells without procesing
Example of a superantigen
Toxic shock syndrome toxin
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
Number of TCR which can bind a MHC/antigen complex
Well under 0.01%
Number of TCR stimulated by a superantigen
Between 1-10% of TCR, depending on which Vbeta is stimulated by superantigen
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
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
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
TCR alpha locus structure
Va1 | VaN | VaJ | Ca
TCR beta locus structure
Vbeta1 | VbetaN | VbetaD1 | VbetaJN | C beta | VbetaD2 | VbetaJN | Cbeta