T Cell Receptors- L8 Flashcards Preview

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Flashcards in T Cell Receptors- L8 Deck (19):
1

CD8 positive T cells target:

A virus infected cell

2

CD4 positive T cells role

Interact with macrophages to produce cytokines and also interact with B cells to produce cytokines. Can signal a B cell to terminally differentiate into a plasma cell.

3

T cell receptor composition

-Alpha chain and beta chain
-Variable region
-Constant region
-Transmembrane region and cytoplasmic tail

4

Biochemical characterization of TCR

1. Disulfide linked heterodimer
2. Both chains are glycoproteins
3. Transmembrane protein only. NO soluble form.
4. Constant and variable regions

5

CD3 role in TCRs

Important in binding TCR to the membrane. They are closely related. The TCR-CD3 complex can participate is signal transduction events.

6

Generating a diverse TCR Repertoire mechanisms

-Recombination of different gene segments (VDJ)
-Recombination of numbers of gene segments (TCRdelta locus)
-Imprecise joining of gene segments
-P and N nucleotide addition (TdT)
-Assembly of different combinations of rearranged TCR chains (alpha and beta or gamma and delta)
-NO somatic mutations!!!!!!!!

7

Components of alpha:beta TCRs

-Variable segments in both
-Diversity segments only in beta chain
-Joining segments in both
-Overall higher diversity in TCR than in BCR

8

Alpha:beta TCRs recognize:

-Short peptide fragments generated from antigenic proteins presented by MHC molecules

9

MHC class 1 molecule

-Most variability occurs in groove region
-Alpha chain is not covalently associated with beta chain.
-Beta chain stabilizes alpha chain on the surface of the cell.

10

MHC class 2 molecule

-Longer peptides than class 1
-Most polymorphism in the beta1 domain.
-NO polymorphism in the alpha2 or beta2 domain.
-Beta is covalently associated unlike class 1

11

Requirements for recognition by a T cell

TCR must see the antigen plus a non-foreign MHC

12

MHC class 1 expression

-All nucleated cells in the body
-Present to CD8 positive T cells

13

MHC class 2 expression

-Antigen presenting cells
-Present to CD4 positive T cells

14

Cytosolic pathogens

-Bind to MHC class 1
-Presented to CD8 T cells
-Causes death of the presenting cell

15

Intravesicular pathogens

-Bind to MHC class 2
-Presented to CD4 T cells
-Activation to kill intravesicular bacteria and parasites

16

Extracellular pathogens and toxin

-Degraded in endocytic vesicles
-Bind to MHC class 2
-Presented to CD4 T cells
-Activates B cells to secrete Ig to eliminate extracellular bacteria and toxins

17

Processing of antigen by class 1 MHC

-Newly synthesized proteins are ubiquinated, then fragmented into peptides by the proteasome
-Peptides attach to TAP protein in the membrane of the ER
-Complex moves into the lumen of the ER and peptide is place in binding groove of MHC class 1
-Peptide travels to cell surface

18

Processing of antigen by class 2 MHC

-Ingested antigens are taken into phagolysosome and fragmented by proteases
-Peptides move to endosomal compartments and placed in binding groove of MHC class 2
-CLIP is displaced and the the complex is carried to the cell surface
-Note: CLIP binds MHC class 2 to prevent the binding of self-peptide fragments

19

Superantigens

-Can act as bridge between TCR and MHC and stimulate high percentage of T cells bearing certain V genes
-Bacterial enterotoxins, minor lymphocyte stimulating antigens, unidentified endogenous antigens
-No requirements for recognition of a peptide
-Ex: toxic shock syndrome is so devastating because it activates so many T cells so quickly