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 a Functional 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 TCR  has 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

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 kDa each chain

11 2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-MHC and 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-2K b CDR1 & CDR2 of V  CDR3 of V  Ternary Complex of TCR Bound to H-2K b and Peptide

MHC Molecule Viewed from Above TCR-V  TCR-V  Peptide

Alloreactivity of T Cells

The End