1 / 29

Self-MHC restriction of the T cell receptor

Self-MHC restriction of the T cell receptor. Self-MHC restriction of T C cells. R. Zinkernagel & P. Doherty. Cloning of the TCR b -chain gene by subtractive hybridization. By S. M. Hedrick & M. M. Davis. 3 important assumptions made by Hedrick and Davis:.

kyrene
Download Presentation

Self-MHC restriction of the 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. Self-MHC restriction of the T cell receptor

  2. Self-MHC restriction of TC cells R. Zinkernagel & P. Doherty

  3. Cloning of the TCR b-chain gene by subtractive hybridization By S. M. Hedrick & M. M. Davis

  4. 3 important assumptions made by Hedrick and Davis: • The TCR mRNA would be associated with membrane-bound polyribosomes like the mRNAs that encode other integral membrane proteins. (eliminate ~97% mRNAs) • 98% of the genes expressed in lymphocytes are common to B and T cells. TCR should be in the 2% genes expressed specifically in T cells. (DNA subtractive hybridyzation eliminates 98%) • TCR genes should undergo DNA rearrangements like those observed in the Ig genes of B cells.

  5. Structure of the ab T-cell receptor and surface IgM

  6. Difference in the structures of the ab and gd receptors

  7. Limited diversity

  8. Organization of mouse TCR gene segments A productive rearrangement of the a chain gene segments deletes Cd

  9. TCR variable- region genes rearrange in a manner similar to Ig gene

  10. Junctional diversity

  11. The CDR3 of the TCR has greater diversity than that seen in immunoglobulins

  12. T-Cell Receptor Complex: TCR-CD3 or ζη CD3 is required for membrane expression of T cell receptors

  13. Structures of the CD4 and CD8 coreceptors or aa dimer

  14. CD8 binds to class I by contacting MHC class I a2 and a3 domains

  15. CD4 binds to class II through MHC class II a2 and b2 domains

  16. Affinity of TCR for peptide-MHC complexes is weak compared with antibody binding T cell-APC interactions are strengthened by cell-adhesion molecules, including CD2, LFA-1, CD28, and CD45R

  17. Role of coreceptors in TCR binding affinity

  18. The ternary complex Of mouse TCR Bound to MHC Class I and peptide CDR3 CDR3

  19. MHC molecule viewed from above not in contact with peptide

  20. CDR regions of mouse TCR a and b chains viewed from above

  21. TCRs interact differently with class I and class II moleucles

  22. Alloreactivity of T cells: in addition to self-MHC plus antigens, T cells also respond to foreign MHC molecules, a reaction that leads to rejection of allogeneic grafts (transplants in the same species) • Alloantigens: epitopes present on molecules that differ among members of the same species because of genetic variation. • T cells recognize a foreign MHC molecules directly. ~1-5% of all T cells are reactive to alloantigen.

More Related