T Cell Receptors- L8 Flashcards Preview

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

CD8 positive T cells target:

A virus infected cell


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.


T cell receptor composition

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


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


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.


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!!!!!!!!


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


Alpha:beta TCRs recognize:

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


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.


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


Requirements for recognition by a T cell

TCR must see the antigen plus a non-foreign MHC


MHC class 1 expression

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


MHC class 2 expression

-Antigen presenting cells
-Present to CD4 positive T cells


Cytosolic pathogens

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


Intravesicular pathogens

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


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


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


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



-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