6 T-Lymphocytes And Antigen Recognition Flashcards
Q: Which immune system cells monitor what is happening inside cells?
A: T lymphocytes (regulatory)
Q: What main components make the T cell receptor? (2) Another subset? What else is present in all? role?
A: Has alpha and beta components which have short cytoplasmic tails
A small subset uses gamma and delta chains
There are charged residues in the transmembrane region of the alpha and beta chains that interact with oppositely charged residues in the transmembrane region of CD3 polypeptides
Q: What is CD3? Why is it important? Useful as? Tail type? length? contains?
A: CD3 polypeptides are a constant part of the TCR
- delivery of the signal to the T lymphocyte once the antigen has been recognised.
- useful as a marker because it is present on all T lymphocytes
They have much longer cytoplasmic tails that have motifs containing tyrosine residues
Q: What occurs to CD3 when TCR meets its antigen? (2)
A: PHOSPHORYLATION OF TYROSINE in the motifs occur -> This triggers several other chemical cascades
ITAM = Immunoreceptor Tyrosine-based Activation Motif
Q: What are the 2 major populations of T cells? What do they do? (3,2)
A: CD4 - antigen presented by MHC Class II - T helper cells (and reg)
Secretes cytokines
Recruit effector cells - activate macrophages
Help and activate CTL and B cell responses
CD8 - antigen presented by MHC Class I - Cytotoxic T Lymphocytes
Kill target cells
Induce apoptosis in target cells
Q: What are CD4 and CD8? role? important in? Key point.
A: CO-RECEPTORS WHICH BIND TO THE SIDE OF THE MHC MOLECULE and increase the avidity of T cell-target cell interaction and are important in signalling
THEY DO NOT BIND TO THE ANTIGEN PRESENTED BY THE MHC, TCR DOES THAT
Q: Describe the main 3 T cells subsets- their process of recognition of an antigen. Role?
A: ‘CD8+ T cell’ = CTL = cytotoxic T lymphocyte -> has CD8 co receptor and a TCR = T cell receptor
Viral infected cells have viral proteins which are processed and presented on MHC Class I for recognition by CD8+
TCR binds to the MHC and the CD8 binds to the side of the MHC
‘CD4+ Th1’ = T helper cells 1
Involved in inflammatory responses
Activates the macrophages so they can kill phagocytosed material
‘CD4+ Th2’ = T helper cells 2
Important in helping B cell response
It captures the antigen on the BCR and takes up the antigen
The antigen is processed an fragments are presented on the MHC Class II
Th2 binds and activates the B cell so it starts producing a response
Q: T cell progenitor cells are from? Begin as? Head to? Arrival they have? Process? (3) Result?
A: Progenitor cells move from the bone marrow to the thymus
They begin as immature thymocytes in the cortex
As they develop they move towards the medulla where they become mature thymocytes
When the precursors arrive at the thymus, they have NO TCR, CD4 or CD8 - there are no co-receptors or antigen specific receptors
1. Rearrangement of the gene segments takes place to form the antigen specific receptor In relation to the TCR: Beta chain is rearranged Alpha chain is rearranged Proper alpha-beta TCR is formed
- If it works thus far - it starts expressing both CD4 and CD8
- Final Selection Stage: You see which MHC molecule it recognises and dependent on this it ends up as either CD4+ or CD8+
Q: Describe alpha and beta chain rearrangement to form the TCR. How is diversity achieved?
A: germline DNA –recombination–> rearranged DNA -> mRNA -> protein (TCR) = occurs to both alpha and beta and comes together
Similar to how antibody diversity is generated but with different gene segments
Beta chain is rearranged FIRST
Beta chain has VDJ
Alpha chain is rearranged SECOND
Alpha chain has VJ
Diversity is achieved by randomly selecting from the gene segments available
Q: What are the 2 checkpoints during T lymphocyte maturation? 3 conclusions. 2 selection types.
A: 1- Pre TCR checkpoint- is the new beta chain functional?
Beta chain rearranges first
If functional it goes on to the next stage
If not, death by apoptosis
2- is the alpha beta TCR functional?/ dangerous?/autoreactive? (against own cells)
Does the TCR recognise self MHC?
If it doesn’t recognise the MHC then it is USELESS
If it binds too tightly to the MHC in the absence of antigen then it is DANGEROUS (NEGATIVE SELECTION= removes said cells that bind too strongly)
If you get something in between it is USEFUL (POSITIVE SELECTION= survival of cells whose TCR recognises self MHC
Q: What percentage of thymocytes survive selection?
A: 5
Q: What do T lymphocytes recognise? What receptor do they have? Where is the receptor derived? Where are they selected for usefulness? What are the 3 main subsets?
A: Recognise peptides presented on the cell surface by MHC molecules
Have an antigen specific receptor derived by rearrangement of gene segments during development in the thymus.
Are selected for usefulness in the thymus
Three Main Subsets:
CD4+ Th1
CD4+ Th2
CD8+ CTL
Q: What is the structure of MHC class I? Draw.
A: brackets below are domains
peptide binding region (alpha 1 and 2)
immunoglobin like region (beta2-microglobin and alpha 3)
transmembrane region
cytoplasmic region
Two Separate Chains: Alpha Chain (polymorphic) - Heavy and beta 2-microglobulin (same in everyone) - Light
The light chain (B2-microglobulin) associates NON-COVALENTLY with the alpha chain
Peptides bind between the alpha-1 and alpha-2 domains
NOTE: B2-microglobulin is NOT TRANSMEMBRANE
Q: What family are MHC a part of? Why?
A: Both domains are immunoglobulin like domains so MHC are part of the immunoglobulin superfamily
Q: What is the structure of MHC class II? Draw.
A: brackets below are domains
peptide binding region (alpha 1 and beta 1)
immunoglobin like region (alpha 2 and beta 2)
transmembrane region
cytoplasmic region
Similar in structure of MHC Class I
DIFFERENCE: There are two polypeptides of equal size which are BOTH transmembrane
There is an alpha chain and a beta chain which are equal in size
Peptide binds between alpha-1 and beta-1
