Structure of T Cell Receptor CHO Variable region “V” Constant region “C” Hinge “H ”...

13
Structure of T Cell Receptor CHO CHO CHO CHO Variable region “V” Constant region “C” Hinge “HAlpha chain Beta chain Disulfide bridge Transmembrane region Cytoplasmic tail + + +
  • date post

    19-Dec-2015
  • Category

    Documents

  • view

    219
  • download

    4

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.

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 2: Structure of T Cell Receptor CHO Variable region “V” Constant region “C” Hinge “H ” Alpha chain Beta chain Disulfide bridge Transmembrane region Cytoplasmic.

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

Page 3: Structure of T Cell Receptor CHO Variable region “V” Constant region “C” Hinge “H ” Alpha chain Beta chain Disulfide bridge Transmembrane region Cytoplasmic.

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.

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.

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

Page 6: Structure of T Cell Receptor CHO Variable region “V” Constant region “C” Hinge “H ” Alpha chain Beta chain Disulfide bridge Transmembrane region Cytoplasmic.

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

Page 7: Structure of T Cell Receptor CHO Variable region “V” Constant region “C” Hinge “H ” Alpha chain Beta chain Disulfide bridge Transmembrane region Cytoplasmic.

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

Page 8: Structure of T Cell Receptor CHO Variable region “V” Constant region “C” Hinge “H ” Alpha chain Beta chain Disulfide bridge Transmembrane region Cytoplasmic.

CD3 Complex With TCR

α β

++

+

δε εγ

ζ ζ

-- - -

TCR

CD3 CD3

Recognition

Signaling

Page 9: Structure of T Cell Receptor CHO Variable region “V” Constant region “C” Hinge “H ” Alpha chain Beta chain Disulfide bridge Transmembrane region Cytoplasmic.

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

Page 10: Structure of T Cell Receptor CHO Variable region “V” Constant region “C” Hinge “H ” Alpha chain Beta chain Disulfide bridge Transmembrane region Cytoplasmic.

Accessory Molecules

• All are invariant

• Increase adhesion between two engaged cells

• Some show increased expression in response to cytokines

Page 11: Structure of T Cell Receptor CHO Variable region “V” Constant region “C” Hinge “H ” Alpha chain Beta chain Disulfide bridge Transmembrane region Cytoplasmic.

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)

Page 12: Structure of T Cell Receptor CHO Variable region “V” Constant region “C” Hinge “H ” Alpha chain Beta chain Disulfide bridge Transmembrane region Cytoplasmic.

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

Page 13: Structure of T Cell Receptor CHO Variable region “V” Constant region “C” Hinge “H ” Alpha chain Beta chain Disulfide bridge Transmembrane region Cytoplasmic.

Interactions of Tc Cell and Target Cell

LFA-1 TCR

CD8

ICAM-1 Class IMHC

LFA-3

LFA-2T cytotoxiclymphocyte

Targetcell

peptide