1 / 36

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)

hollis
Télécharger la présentation

Chapter 9 T-Cell Receptor

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  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

More Related