T Cells And TCRs Flashcards
Where does T cell development occur
Produced in bone marrow
HSC precursor —> thymus to mature (thymocytes)
What does T cell maturation involve
Rearrangement of TCRs
Positive and negative selection (central tolerance)
What is central tolerance
Positive and negative selection
Surviving: thymocytes that recognise MHC I/II —> MHC restriction (positive)
Apoptosis: thymocytes that bind to self-peptides/MHC I/II complexes (negative) —> self tolerance
Describe the processes involved in T cell maturation
- T cells rearrange TCRs genes
- Expression of TCR (alpha-beta or gamma-delta chains)
- Expression of both CD4 and CD8 co-receptors
- Double positive (selection)thymocytes
- generation of single positive thymocytes expressing TCR
What is a Double negative thymocytes
Expresses neither CD4 or CD8
What is a Double positive thymocyte
Express both CD4 and CD8
What is a single positive thymocyte
Expresses one of either CD4 or CD8
What is cluster differentiation (CD(4))
Membrane glycoproteins
Which type of CD molecules do MHC II cells bind to
CD4
Rule of 8, (MHC) 2 x (CD)4 = 8
Which type of CD molecules do MHC I cells bind to
CD8
Rule of 8, MHC (1) x CD(8) = 8
What are TCRs
- Membrane bound glycoproteins similar to Fab fragment
- 2 polypeptide chains: alpha-beta or gamma-delta
- 3 regions: variable V, Constant C and membrane anchoring
- Recognises only protein antigens presented on host cells by MHC I
- T cells DO NOT produce soluble or antigen like molecules
Describe the TCR-alpha locus
Chromosome 14
70-80 V-alpha genes
61 J-alpha gene segments
1 C gene
Describe the TCR beta locus
Chromosome 7
52 V-beta genes
2x (1D gene, 7J genes, 1C gene)
Explain TCR diversity
VDJ recombination - TCRalpha locus: VJ recombination - TCRbeta locus: VDJ recombination of alpha and beta chains Junctional Diversity NO somatic hypermutation
Functions of TCR
Naive TCRs and APC —> signalling cascade —> enhanced T cell cervical —> proliferation —> differentiate into distinct effector and memory Tc and Th subtypes