Zusammenfassung der Ressource
T cell
receptors
- Bone marrow dervied lymphocytes, mature
in thymus, express the CD3-TCR complex.
- 2 Forms: αβ found on CD4+ve T helper cells and
CD8 cytotoxic cells/ γδ TCR 1-10% of T cells
- T cell receptors are clonally distributed,
generated by somatic recombination
- Structure of αβ TCR- 3
hypervariable regions directly
involved in Ag binding.
- Both forms of the TCR receptor are associated wirh rh polypeptide of the CD3
complex.CD3= 4 Invariant polypeptides necessary for TCR surface expression
which act in signal transduction following specific Ag recognition by the TCR.
- Ag recognition
- T cells recognise Ags presented by other cells in the
body. Do not bind free or soluble Ags like Abs
- For αβ TCRs-Ags are recognised as short peptides 9-13AA, along
with the MHC molecule. Only recognises when bound to MHC
- γδ Ag recognition less understood
- CD4+ve T helper-Class II/ CD8+ cytotoxic-class
I. Specificity at level of the T cell not MHC
- Somatic recombination
- =T cell diversity. In
the thymus during
T cell differentiation
- Mechanistically
rearrangrment of the
TCR genes resembles
that of the Ig gene but
with some subtle
differences.
- Alpha rearrangement
- ~75 variable, 61 joining, 1
constant- rearrangement to
form VJ-txn-trans=polypeptide
- ~5000
- Beta rearrangement
- 60 variable, diversity, joining and
constant-DJ rearrangement followed by
VDJ second rearrangement=polypeptide
- ~1,500
- γδ TCR genes- δ is located within the α gene loci
- 60 y & ~150 δ
- Junctional diversity
- Nibbling of several bases at 3' end of V gene and
5' end of D/J gene=imprecise joining. Up to 3
'palindromic' nucleotides can be added: Insertion
of up to 10 random bases, not coded by TCR
genes=N-region addition. Dδ gene segments can
be read in all three reading frames
- T cell diversity αβ- combinatorial diversity gives (5000 x 1500)= 10^7 + junctional diversity= 10^10
- T cell diversity γδ- combinational diversity (60 x 150)= 9000 + junctional diversity=much higher
- Gene rearrangement in the thymus
- recombination signal sequences
regulate rearrangement of gene
segments. Heptamer-nonomer
sequences seperated by 12/ 23
bases (see sheet).
- Mediated by RAG1 & 2 genes
- more diversity is concentrated at the third hypervariable
region because -terminal deoxytransferase can
randomly add up to 10 nts at all joints -D region genes
can be read in all reading frames (δ gene)
- TCR b, γ & δ gene rearrangements start together
on both chs. Producxtive rearrangements supress
further rearrangement of homologous chs- TCR a
genes rearranged last
- T cell lineage determination
- Interaction of TCR with MHC + peptide
- V regions including CDRs 1 + 2 interact
with MHC. (D-)J regions comprising CDRs3
interact with MHC bound peptide