Antigen recognition: T cells and MHC Flashcards
What are the equivalent of antibodies on T cells?
T cell receptors
How are T cells different from B cells?
T cells carry different receptors
T cells are encoded by different loci
B cells evolved after T cells
What evidence is there that B cells are more evolved that T cells?
T cells are found in simpler animals
How are the T cell receptors structurally different from B cell receptors?
TCR is made up of alpha and beta chains
BCR are made of a dimer of dimers
What is referred to when we say T cell receptors?
Receptors that specifically recognise antibodies
NOT the receptors for different cytokines and antibodies
How are BCR and TCR fundamentally different?
TCR are solely transmembrane
BCR can be secreted
TCRs are heterodimers, BCRs are dimers of dimers
Which mechanism of diversity exists in BCR but not TCR generation?
Somatic hypermutation
Which mechanisms of cell diversity are similar to B cells?
Multiple germline genes
V-J and V-D-J recombination
Recombinational inaccuracies
N-nucleotide addition
Chain combination
Describe the evolution of TCRs and BCRs
T and B cells are homologous
This is made obvious by their similarities
They are derived from one common ancestral gene that later evolved separately
How many times has the locus producing the T cell receptors evolved?
At least 3 times
What are the two types of TCRs found on T cells?
TCR ab
TCR gd
How are the two types of TCR different?
TCR ab is very common, occupying 50% of circulating lymphocytes
TCR gd is expressed by a distinct population of T cells with less variability than ab T cells, since there are less genes coding for them
What is the difference between the ways BCR and TCR recognise antigens?
BCR complementarity depends on the shape of the antigen
TCR complementarity does not depend on 3D shape, but rather recognises sequences of the antigen
Why is the way TCRs recognise antigens more efficient?
The shape of an antigen changes very readily as it evolves, so a recognition system based on this is not very efficient
T cells recognises smaller pieces of the pathogen which are difficult to change
What are MHCs?
Major Histocompatibility Complexes
Molecules which act to bind to the highly unstable peptides which T cell receptors recognise
What is another name for MHCs?
HLA
MHCs in humans
What is the shape of MHCs?
Single alpha chain composes the whole structure
Beta-2 microglobulin holds the structure together
Contain grooves where the antigen fits into
What is the shape of the groove antigens fit onto the MHC through?
Two a-helices
A b-pleated sheet floor
What happens when the peptides bind to the MHC?
Peptide becomes deeply embedded
Becomes an intrinsic part of the structure
Without it, the MHC is unstable
What do T cell receptors recognise?
T cells can only detect the amino acids exposed through the MHC
This hospot (antigen + MHC) is detected as non-self
So the TCR recognises the composite structure formed by the mixture of self (MHC) and non-self (viral/bacterial peptide)
What type of binding occurs between the MHC hotspot and the TCR?
Covalent bond
Must be tightly controlled in order to retain the characteristic weak binding that remains a feature of T cells
This allows T cells to leave once bound to its target
How specific must the MHC binding groove be?
The specificity must be tightly controlled
If it is too specific, no peptide would bind to it
If it is too broad, no peptide would bind strongly enough
One MHC binds to one peptide
TRUE or FALSE
FALSE
One MHC binds to a lot of different peptides
MHC have pockets which only take amino acids which fit in specific positions
Investigations have shown the peptides that fit to a specific MHC have some similarities between them
What type of interaction occurs between the MHC and the peptide?
Non-covalent
What type of interaction occurs between the MHC hotspot and the T cell?
Covalent
Which chromosome codes for MHC?
Chromosome 6
What are the two types of MHC?
MHC I
MHC II
How many genes code for MHC I? What are they called?
3 genes
A, B and C
Which cells carry MHC I on their surface?
All nucleated cells
Therefore, at any rate, the T cell can recognise the infection of any cell of the body
Examples of classical genes that code for HLA I
DPB2
DPA1
How many different molecules form part of class II MHC?
3
Divided into DP, DQ and DR
How is MHC variability increased?
Number of variants in each gene that code for HLA molecules
Each individuals inherits 2 HLA molecules which are codominantly expressed on each cell
Different subtypes of each HLA
Which T cells recognise MHC II?
CD4 T cells
Which T cells recognise MHC I?
CD8 T cells
What is exogenous processing?
The process by which APCs present antigens on the MHC II following phagocytosis
Describe the process of exogenous processing
The MHC II is made in the golgi
It is transported through vesicles and transformed in the process through the addition of sugars
MHC II meets the peptides are found in the loading compartment (endosomes)
Within the endosomes, proteins are cleaved and bound to the MHC
Then it becomes presented on the surface of APCs
What is the target of CD4 T cells?
MHC II presenting peptides
On APCs
What is endogenous processing?
Process of presenting peptides made intracellularly
Onto MHC I
Describe the process of MHC I exogenous processing
MHC I are produced in the endoplasmic reticulum
A protein becomes degraded by the proteasome, and enters the endoplasmic reticulum through TAP proteins
The intracellular proteins bind to MHC inside the endoplasmic reticulum
The MHC I-antigen complex travels to the cell surface through the Trans-Golgi vesicle
What are the two main differences between exogenous and endogenous processing?
Loading compartment
- MHC II = endosome
- MHC I = endopasmic reticulum
Peptide origin
- MHC II = exogenous
- MHC I = endogenous
What does the MHC I bind to?
The peptides the MHC recognises are produced by the same cell making the MHC
What is the purpose of the T cell receptor?
Signalling the cell to divide and differentiate to provide memory and effector function
Can TCRs function on their own?
No
They need accessory molecules
CD3
These transduce the signal in the cell and cause differentiation upon binding of the antigen to the TCR
Without costimulatory molecules, binding of the TCR would result in no response
TRUE or FALSE
TRUE
This specific interaction is necessary but not sufficient
Which other costimulatory molecules are important for correct T cell functioning?
CD28
CTLA4
LFA1
What do the costimulatory molecules CD28 and CTLA4 bind to?
CD80/86 on APCS
What is the importance behind CTLA4/CD28 binding to CD80/86
Binding determines whether there is a response or not
Makes sure the response only occurs when needed
What does LFA1 on T cells bind to?
ICAM on APCs
What is the importance behind the LFA1/ICAM bond?
Ensured the cells bind long enough
