Lecture 3 Flashcards
How are T cell receptors encoded?
By rearranging genes
What regions of the T cell receptors are encoded?
Variable regions are encoded by V,D,J segments
Where do b cells develop?
In the bone marrow
Where to T cells go once they have left the bone marrow?
Thymus
When do T cells rearrange?
When in the thymus, don’t turn on until they are in the thymus
When do B cells rearrange?
When in the Bone marrow
What are some similar mechanisms that are seen in in TCR that are also in BCR?
Multiple V,D and J gene segments, combinatorial diversity and junctional diversity
Unlike a BCR what is never done in a TCR?
It is never secreted it is always found on the surface of the cell
What else is not found in the T cell?
Hyper mutation
What happens randomly in T cells?
An individual T cell will breaks its DNA randomly during the alpha D and V region
What to alpha and beta chains do?
Pair up to combine together to make a unique T cell receptor in the cell
What is T cell alpha chain similar to?
Light chain
What is the T cell beta chain similar to?
Heavy chain
Why do T cells not have hyper mutation?
Because the don’t contain AID (activation induced cytidine deaminase
On the beta chain what binds first?
D and J chain then they combine with a v chain
Where does splicing occur on a T cell?
Constant region
Where do TCR recognise antigens?
In grooves of MHC molecules
Where is the single alpha chain located?
On chromosome 14
What will T cells generate?
Either alpha beta cell receptors or gamma delta cell receptors
What are the gene segments found in a TCRbeta?
V,D,J,C
What are the gene segments found on TCRalpha?
V,J,C
Where is HLA found?
On chromosome 6
How are MHC expressed?
Co-dominantly
What do class I MHC molecules express?
All nucleated cells
What do class II MHC molecules express?
Expressed on only particular cell types
What are the specific types of cells that MHC class II molecules express?
B cells, macrophages, dendritic cells
What are MHC molecules induced by?
Interferons (inflammation)
How many MHC molecules will a single gene contain?
12 MHC molecules
What is the gene structure of class I MHC molecules?
HLA-A, HLA-B, HLA-C
What is the gene structure for class II MHC molecules?
HLA-DP, HLA-DQ, HLA-DR
What do class II molecules contain?
Maternal and paternal expression
If there is one heterozygous gene at each loci how many class I molecules can be expressed?
6 different class I molecules
What is the co-dominant expression of MHC molecules?
Polymorphism and polygeny
Where do polymorphism occur?
In clusters
Where does the variability of MHC molecules occur?
Occur where the MHC forms the peptide binding groove
What are regions for such high levels of MHC polymorphism?
Binding of a vast range of peptides that be presented to T cells
What is the downside of high levels of MHC polymorphism?
Increased immune-mediated disease e.g. increases the likelihood of presenting self antigens (could state an immune response on yourself)
Where are antigens from?
Either from inside the cell or from a pathogen that has hijacked a cell
Endogenous?
Inside the cell - will end up on the source of the cells by class I
Exogenous?
Outside the cell - bacteria that float around outside cells get taken up by the cells - MHC class II
What do macrophages do?
They eat antigens and display them on its surface
How do peptides end up on the surface of the cells bound to MHC molecules?
The are PROCESSED into small peptide fragments suitable for binding to and presentation by MHC I and II
What does the proteasome do to antigens?
Degrade and chop up the antigens in the cytoplasm
Where are class I molecules found?
In the ER
What does the proteasome allow the fragments in the ER to do?
Bind to peptide binding grooves which allows class I molecules to go out of the ER into the cell surface
Where is the viral protein synthesised in class I?
In the cytoplasm
How are the peptides transported in class I?
By the TAP transporter - to ER
What happens once the peptides bind to the class I molecules?
Transported to the cell surface
What can the proteasome change?
Can change its behaviour depending on what happens outside the cell
What is TAP TRANSPOTER?
A component of multi protein assembly
What does the TAP component contain?
Contains tapasin and calreticulin
Where is the bacteria (antigen) found in the MHC II molecule?
Endocytosed into intracellular vesicles inside the cell
How is the protein cleaved to peptides in MHC II?
By acid proteases in vesicles
Where is class II targeted?
Targeted in the endocydic pathway
Why aren’t class II molecules loaded into the ER?
Because the invariant chains stops this from happening
What does the invariant chain do?
Binds to the class II peptide binding groove blocking the peptides from getting into the ER
What happens to the lysosomal enzymes in the endocydic pathways (MHC class II)
They get degraded leaving the CLIP peptide associated with the binding groove
What can displace the CLIP?
Peptides from the antigen
What is HLA-DM required for?
Loading peptides into the groove
What happens in normal healthy uninfected cells?
MHC I and II will bind and present peptides from self proteins
What are LMPs?
They are molecules part of the proteasome - change change the features of the proteasome
What can class I molecules be killed by?
CD8+ (cytotoxic cells)
What are MHC II cells also known as?
APC (antigen presenting cells)
What are some example of antigen presenting cells?
Macrophages, dendritic cells and B cells
What cells can express MHC class II cells?
CD4 T helper cells
