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Chapter 9 T-Cell Receptor
Self-MHC Restriction of the TCR
Structure of TCR
Structural Similarity between TCR and mIgM
Resembling Fab?
Organization and Rearrangement of TCR Genes
Identifying and Cloning the TCR Genes (Hedrick and Davis, 1984)
- TCR mRNA represents a minor fraction of the total cell mRNA.
Well-thought-out assumptions of TCR Genes : 1. mRNAs are associated with membrane-bound polyribosomes rather than with free cytoplasmic ribosomes. 2. mRNAs are only expressed in T, but not in B cells. subtractive hybridization (98% of the genes expressed in T and B cells are the same)
3. DNA is rearranged in mature T cells.
~ 2% of total cDNA
Germ-line Organization of the Mouse TCR -, -, -, and -chain Gene Segments
Gene Rearrangements That Yield aFunctional Gene Encoding the TCR
The C region of TCR is much simpler than the C region of Ig genes:
- TCR is expressed only in a membrane-bound form; thus, no differential RNA processing is required to produce membrane and secreted form.
- TCR has only a single C gene segment and TCRhas two C gene segments.
- No known functional differences exist in C regions.
- Mechanisms of V-region rearrangements of TCR genes are very similar to those of Ig genes.
- Although B cells and T cells use very similar mechanisms for V-region gene rearrangements, the Ig genes are not rearranged in T cells and the TCR genes are not rearranged in B cells.
- Presumably, the recombinase enzyme system is regulated in each cell lineage, so that only rearrangement of the correct receptor DNA occurs.
- A region within the chain 3’ end enhancer can suppress the rearrangement of -chain genes in T cells.
Domains and CDRs of -TCR
Generation of TCR Diversity
TCR Ig
The location of one-turn (12-bp) and two-turn (23-bp) recognition Signal sequences in TCR - and -chain
DNA differs from that in Ig H-chain DNA
Or V-D-D-D-J
Generate considerable additional diversity in TCR genes.
TCR Ig
TCR Ig
T-Cell Receptor Complex: TCR-CD3
or
(immunoreceptor tyrosine-based activation motif)
B-cell Receptor
ITAM
T-Cell Accessory Membrane Molecules
CD4 and CD8 Coreceptors
55-kDa
30-38 kDa each chain
1
2
Interaction of CD8 Coreceptor with TCR and Class I MHC Molecule
Interaction of CD4 Coreceptor with TCR and Class II MHC Molecule
CD4 Interacts with a Dimer of Class II MHC Molecules
A Lattice-type Structure formed by Interaction of CD4 and Class II MHC
Affinity Constants for Various Biological Systems
Interactions between TCR/Peptide-MHCand Accessory Molecules/Ligands
HLA-A2
HTLV-1 tax peptide
Interaction between TCR and HLA-A2 with bound HTLV-I Tax Peptide
TCR
CDR1 & CDR2 of V
CDR3 of V
peptide
H-2Kb
CDR1 & CDR2 of V
CDR3 of V
Ternary Complex of TCR Bound to H-2Kb and Peptide
MHC Molecule Viewed from Above
TCR-V
TCR-V
Peptide
Alloreactivity of T Cells
The End