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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:.

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Self-MHC restriction of the T cell receptor

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  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.

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