Structure of T Cell Receptor CHO Variable region “V” Constant region “C” Hinge “H ”...
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Transcript of Structure of T Cell Receptor CHO Variable region “V” Constant region “C” Hinge “H ”...
![Page 1: Structure of T Cell Receptor CHO Variable region “V” Constant region “C” Hinge “H ” Alpha chain Beta chain Disulfide bridge Transmembrane region Cytoplasmic.](https://reader034.fdocument.pub/reader034/viewer/2022051618/56649d395503460f94a1352e/html5/thumbnails/1.jpg)
Structure of T Cell Receptor
CHO CHO
CHOCHO
Variable region “V”
Constant region “C”
Hinge “H”
Alphachain
Betachain
Disulfide bridge
Transmembrane region
Cytoplasmic tail
++ +
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Structure of T Cell Receptor (TCR)
• Two polypeptide chains, α and β, of roughly equal length
• Both chains consist of a variable (V) and a constant (C) region
• α chain V region has a joining (J) segment• β chain V region has both a J and diversity
(D) segment
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Structure of T Cell Receptor(continued)
• Hypervariable regions in V contribute to diversity of TCR
• TCR recognizes portions of MHC molecule and peptide bound in the groove
• Small population of T cells has a TCR comprised of γ and δ chains – γδ TCR specificity differs from αβ TCR
![Page 4: Structure of T Cell Receptor CHO Variable region “V” Constant region “C” Hinge “H ” Alpha chain Beta chain Disulfide bridge Transmembrane region Cytoplasmic.](https://reader034.fdocument.pub/reader034/viewer/2022051618/56649d395503460f94a1352e/html5/thumbnails/4.jpg)
Structure of T Cell Receptor
CHO CHO
CHOCHO
Variable region “V”
Constant region “C”
Hinge “H”
Alphachain
Betachain
Disulfide bridge
Transmembrane region
Cytoplasmic tail
++ +
![Page 5: Structure of T Cell Receptor CHO Variable region “V” Constant region “C” Hinge “H ” Alpha chain Beta chain Disulfide bridge Transmembrane region Cytoplasmic.](https://reader034.fdocument.pub/reader034/viewer/2022051618/56649d395503460f94a1352e/html5/thumbnails/5.jpg)
Properties of Ig and TCR Genes
Ig TCR
Many VDJs, few Cs yes yes
VDJ rearrangement yes yes
V-pairs form antigen yes yes recognition site
Somatic hypermutation yes no
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Properties of Ig and TCR Proteins
Ig TCR
Transmembrane forms yes yes
Secreted forms yes no
Isotypes with different yes no functions
Valency 2 1
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CD3 Complex• Group of four proteins associated with TCR
• Consists of a γ, a δ, two ε, and two ζ chains
• All four proteins are invariant
• Functions: 1) synthesized co-ordinately with TCR, required to bring TCR to surface
2) transduces activating signals to T cell when TCR recognizes MHC-peptide
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CD3 Complex With TCR
α β
++
+
δε εγ
ζ ζ
-- - -
TCR
CD3 CD3
Recognition
Signaling
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Accessory Molecules Involved in Cell-Cell Interactions
T cell surface molecules that engage with ligand on 2nd cell when TCR recognizes MHC-peptide
T Cell Ligand on 2nd Cell CD4 class II MHC (β2 domain) CD8 class I MHC (α3 domain) LFA-2 LFA-3 LFA-1 ICAM-1, ICA-2 LFA = Leukocyte Function-associated AntigenICAM = InterCellular Adhesion Molecule
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Accessory Molecules
• All are invariant
• Increase adhesion between two engaged cells
• Some show increased expression in response to cytokines
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Costimulatory Molecules
• Molecules on T cell and 2nd cell that engage to deliver 2nd signal required for activation of T cell
• Most important costimulatory molecules:
T cell Ligand on 2nd cell
CD28 B7-1 (CD80), B7-2 (CD86)
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Interactions of Th Cell and APC
LFA-3
LFA-2 LFA-1 TCR
CD4
ICAM-1 Class IIMHC
B7-1/B7-2(CD80/CD86
CD28
IL-1IL-6TNF-alphaIL-12IL-15
TNF-betaIFN-gammaGM-CSFIL-4
T helperlymphocyte
Antigen-presenting
cell
peptide
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Interactions of Tc Cell and Target Cell
LFA-1 TCR
CD8
ICAM-1 Class IMHC
LFA-3
LFA-2T cytotoxiclymphocyte
Targetcell
peptide