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Chapter 9 T-Cell Receptor

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)

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Chapter 9 T-Cell Receptor

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  1. Chapter 9 T-Cell Receptor

  2. Self-MHC Restriction of the TCR

  3. Structure of TCR

  4. Structural Similarity between TCR and mIgM  Resembling Fab?

  5. Organization and Rearrangement of TCR Genes

  6. 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.

  7. ~ 2% of total cDNA

  8. Germ-line Organization of the Mouse TCR a-, b-, g-, and d-chain Gene Segments d

  9. Gene Rearrangements That Yield a Functional Gene Encoding the ab TCR

  10. 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. • TCRa has only a single C gene segment and • TCRb has two C gene segments. • No known functional differences exist in C • regions.

  11. Mechanisms of V-region rearrangements • of TCR genes are very similar to those • of Ig genes.

  12. 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 k chain 3’ end enhancer can • suppress the rearrangement of k-chain genes in T • cells.

  13. Domains and CDRs of ab-TCR

  14. Generation of TCR Diversity

  15. The location of one-turn (12-bp) and two-turn (23-bp) recognition Signal sequences in TCR b- and d-chain DNA differs from that in Ig H-chain DNA TCR Ig Or V-D-D-D-J  Generate considerable additional diversity in TCR genes.

  16. TCR Ig

  17. TCR Ig

  18. T-Cell Receptor Complex: TCR-CD3 or (immunoreceptor tyrosine-based activation motif)

  19. B-cell Receptor ITAM

  20. T-Cell Accessory Membrane Molecules

  21. CD4 and CD8 Coreceptors 55-kDa 30-38 kDa each chain

  22. Interaction of CD8 Coreceptor with TCR and Class I MHC Molecule a1 a2

  23. Interaction of CD4 Coreceptor with TCR and Class II MHC Molecule

  24. CD4 Interacts with a Dimer of Class II MHC Molecules

  25. A Lattice-type Structure formed by Interaction of CD4 and Class II MHC

  26. Affinity Constants for Various Biological Systems

  27. Interactions between TCR/Peptide-MHC and Accessory Molecules/Ligands

  28. Interaction between TCR and HLA-A2 with bound HTLV-I Tax Peptide HTLV-1 tax peptide HLA-A2

  29. Ternary Complex of TCR Bound to H-2Kb and Peptide TCR CDR1 & CDR2 of Vb CDR3 of Vb peptide H-2Kb CDR1 & CDR2 of Va CDR3 of Va

  30. MHC Molecule Viewed from Above TCR-Vb Peptide TCR-Va

  31. Alloreactivity of T Cells

  32. The End

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