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