T-Lymphocytes and Antigen Recognition Flashcards
What do T lymphocytes monitor?
The inside of cells
Describe the structure of the TCR. What are the subsets.
Related to the Fab part of an antibody. Has a variable, constant and transmembrane region as well as a cytoplasmic tail. Has alpha and beta components but a small subset use gamma and delta (10%).
What molecule is present on EVERY T lymphocyte?
CD3
Key difference between CD3 polypeptide and the TCR?
CD3 polypeptide has a much longer cytoplasmic tail
What happens when the T cell receptor meets its antigen regarding the CD3 polypeptide?
The tails have motifs containing tyrosine residues and when the TCR receptor meets its antigen phosphorylation of the tyrosine occurs
Do both types of T cells secrete cytokines?
Yes
What do T helper 1 target and are involved is?
Involved in inflammatory responses, activates macrophages to kill phagocytosed material
What are T helper 2’s involved in?
Activation of a B cell
Are immature thymocytes found in the centre or outside of the thymus?
Towards the outside
Describe the maturation of the T cell. What do precursors lack when they reach the thymus? Which chain rearrangement takes place first? How are CD4/CD8 expressed?
When the precursors arrive at the thymus, they have NO TCR, CD4 or CD8. Rearrangement of the gene segments for the beta chain takes place and then the alpha chain to form the TCR. Then CD4 and CD8 are expressed (double positive). There is a selection process to see which kind of MHC molecule the cell can recognise, either CD4 by binding to an MHC class II molecule or CD8 aka MHC class I.
How is the beta chain rearranged in the TCR (which components)?
VDJC (remember C is constant region)
How is the alpha chain rearranged in the TCR (which components)?
VJC (remember C is constant region)
How many variable gene segments in the TCR?
5
What needs to be checked to ensure a TCR is functioning? (2)
See if it recognises MHC, makes sure it doesn’t bind too tightly to MHC.
What % of thermocytes survive selection?
5%
What is the structure of MHC I?
Heavy alpha chain, with three domains (2 in the peptide binding region, 1 in Ig like region) and light beta 2 microglobulin chain.
Is the alpha chain polymorphic?
Yes
Is the beta 2 microglobulin chain polymorphic?
No
Is the beta 2 microglobulin chain transmembrane?
No
What is the structure of MHC II?
Alpha and beta chains of equal size that are both transmembrane
Where do peptides bind in MHC II,
Between alpha 1 and beta 1
Which MHC class presents at longer peptides?
MHC class II
What is an MHC binding motif?
The way MHC can present many different peptides but with some specificity. Certain positions tend to be particular amino acids and others could be anything else
What HLA?
Human MHC
What are the three types of class I MHC?
A B and C
What are the three types of class II?
DP, DQ and DR
What chromosome is the HLA genes found on?
6
Is beta 2 microglobulin found on the same chromosomes as the HLA genes?
No
How many different class I and II molecules can we make and why?
6 of each as we are diploid and the HLA genes are codominant.
Which cells express MHC class I and which express class II?
All nucleated cells express I, and only professional APC’s have class II
What is the most polymorphic gene in the human body? What are the consequences of this?
MHC. This means that we all have different responses to the same infection.
What produces endogenous antigens? How are these presented? Which MHC class presents them?
Virus’s. Viral proteins are processed by a multisubunit proteolytic system - proteasome. Peptides then move into the ER via TAP (transporter associated with antigen processing). MHC class I moves into ER. The alpha chain binds with the peptide and the beta 2 microglobulin. Then goes via the Golgi to the cell surface.
What produces exogenous antigens? How are these presented? Which MHC class presents them?
Proteins are endocytosed and processed into peptides in endocytic vesicles. Class II molecules enter ER, and associates with the invariant chain. The invariant chain is the digested as the complex enters the endocytic pathway. You end up with a small peptide fragment bound to MHC II known as CLIP (Class II Associated Invariant Chain Peptide). The CLIP peptide is then swapped for the antigenic peptide. Peptide and MHC II then goes to cell surface.
What is the purpose of CLIP?
Stops peptides that should be going onto class II going onto class I.
