SelfMHC restriction of the T cell receptor

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Self-MHC restriction of the T cell receptor
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Self-MHC restriction of TC cells
R. Zinkernagel P. Doherty
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Cloning of the TCR b-chain gene by subtractive
hybridization
By S. M. Hedrick M. M. Davis
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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.

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Structure of the ab T-cell receptor and surface
IgM
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Difference in the structures of the ab and gd
receptors
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Limited diversity
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Organization of mouse TCR gene segments
A productive rearrangement of the a chain gene
segments deletes Cd
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TCR variable- region genes rearrange in a manner
similar to Ig gene
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Junctional diversity
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The CDR3 of the TCR has greater diversity than
that seen in immunoglobulins
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T-Cell Receptor Complex TCR-CD3
or ??
CD3 is required for membrane expression of T cell
receptors
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Structures of the CD4 and CD8 coreceptors
or aa dimer
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CD8 binds to class I by contacting MHC class I a2
and a3 domains
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CD4 binds to class II through MHC class II a2 and
b2 domains
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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
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Role of coreceptors in TCR binding affinity
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The ternary complex Of mouse TCR Bound to
MHC Class I and peptide
CDR3
CDR3
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MHC molecule viewed from above
not in contact with peptide
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CDR regions of mouse TCR a and b chains viewed
from above
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TCRs interact differently with class I and class
II moleucles
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• 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.