chapter 9 t-cell receptor. self-mhc restriction of the tcr
TRANSCRIPT
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Chapter 9 T-Cell Receptor
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Self-MHC Restriction of the TCR
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Structure of TCR
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Structural Similarity between TCR and mIgM
Resembling Fab?
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Organization and Rearrangement of TCR Genes
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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.
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~ 2% of total cDNA
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Germ-line Organization of the Mouse TCR -, -, -, and -chain Gene Segments
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Gene Rearrangements That Yield aFunctional Gene Encoding the TCR
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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.
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- Mechanisms of V-region rearrangements of TCR genes are very similar to those of Ig genes.
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- 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.
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Domains and CDRs of -TCR
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Generation of TCR Diversity
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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.
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TCR Ig
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TCR Ig
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T-Cell Receptor Complex: TCR-CD3
or
(immunoreceptor tyrosine-based activation motif)
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B-cell Receptor
ITAM
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T-Cell Accessory Membrane Molecules
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CD4 and CD8 Coreceptors
55-kDa
30-38 kDa each chain
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1
2
Interaction of CD8 Coreceptor with TCR and Class I MHC Molecule
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Interaction of CD4 Coreceptor with TCR and Class II MHC Molecule
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CD4 Interacts with a Dimer of Class II MHC Molecules
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A Lattice-type Structure formed by Interaction of CD4 and Class II MHC
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Affinity Constants for Various Biological Systems
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Interactions between TCR/Peptide-MHCand Accessory Molecules/Ligands
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HLA-A2
HTLV-1 tax peptide
Interaction between TCR and HLA-A2 with bound HTLV-I Tax Peptide
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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
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MHC Molecule Viewed from Above
TCR-V
TCR-V
Peptide
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Alloreactivity of T Cells
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The End