Immunology 6: T Lymphocytes and Antigen Recognition Flashcards
Describe T Cell Receptor (TCR)
Related to the structure of antibodies
The variable region interacts with the antigen
Very short cytoplasmic tail
Has alpha and beta components
A small subset uses gamma and delta chains
Diversity in the variable region results by the combination of gene segments (like VDJ recombination)
TCR is a member of the immunoglobulin superfamily
What is the importance of the CD3 polypeptide
CD3 polypeptides are a constant part of the TCR
They are important in the delivery of the signal to the T lymphocyte once the antigen has been recognised.
The tails have motifs containing tyrosine residues
What happens when a tcr meets its antigen
PHOSPHORYLATION OF TYROSINE in the motifs occur
This triggers several other chemical cascades
ITAM = Immunoreceptor Tyrosine-based Activation Motif
TWO MAJOR POPULATIONS OF T cells:
CD4 - MHC Class II
CD8 - MHC Class I
What is the role of CD4 cells
T helper cells
Secretes cytokines
Recruit effector cells - activate macrophages
Help and activate CTL and B cell responses
What is the role of CD8 cells
Cytotoxic T Lymphocytes
Kill target cells
Induce apoptosis in target cells
Describe T cell development in the thymus
(In the cortex)
When the precursors arrive at the thymus, they have NO TCR, CD4 or CD8 - there are no co-receptors or antigen specific receptors
Rearrangement of the gene segments takes place to form
preTCR beta chain
Then CD4 and CD8 are expressed along with a full TCR
(In the medulla)
There is a selection process to see which kind of MHC molecule the cell can recognise
Depending on which type of MHC they recognise, they will either become CD4+ or CD8+
How are the different TCR receptor alpha and beta chains formed
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
Define Major Histocompatibility Complex
a group of tightly linked genes that are important in specific immune responses.
MHC Class I Structure
Two Separate Chains:
Alpha Chain - Heavy
b2-microglobulin - Light
Alpha Chain = POLYMORPHIC
B2-microglobulin = SAME IN EVERYONE
The light chain (B2-microglobulin) associates NON-COVALENTLY with the alpha chain
Both domains are immunoglobulin like domains so MHC are part of the immunoglobulin superfamily
Peptides bind between the alpha-1 and alpha-2 domains
MHC Class II Structure
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
Where do CD4 and CD8 bind
CD4 and CD8 ARE CO-RECEPTORS WHICH BIND TO THE SIDE OF THE MHC MOLECULE - THEY DO NOT BIND TO THE ANTIGEN PRESENTED BY THE MHC, TCR DOES THAT!
Which MHC present the shorter peptide
MHC Class I presents peptides that are 8-10 amino acids long - SHORTER PEPTIDES
MHC Class II presents longer peptides (13+ amino acids) - LONGER PEPTIDES
Ends of the peptide often sticks out of the peptide binding site on the MHC.
How are polypeptides binded to MHC
They do this by having certain positions on the MHC that are relatively CONSERVED that anchor the peptide into BINDING POCKETS in the MHC.
There are binding pockets within the MHC molecules - within the peptide there will be certain positions that are always more or less exactly the same amino acid.
This is known as a BINDING MOTIF
This means that MHC presents a subset of peptides which have some things in common where characteristics are conserved.
What is the MHC in humans called?
The HLA (Human Leukocyte Antigen) region
Describe the Human Leukocyte Antigen
The polypeptides that make up the MHC molecules are encoded within the HLA region
Three types of Class I = A, B and C
Three types of Class II = DP, DQ and DR
In class I it is only the heavy chain that is encoded within HLA - B2-microglobulin is encoded on a different chromosome
We are diploid so we have two sets like this meaning that we can have up to SIX different class I and class II molecules
MHC Gene Expression
MHC is polygenic - there are several class I and class II loci
It is CODOMINANT - maternal and paternal genes are both expressed
MHC Class I - nearly ALL CELLS - expression varies during infection or by cytokines
MHC Class II - only on PROFESSIONAL APCs - regulated by cytokines
Are MHC same in everyone
no
MHC IS HIGHLY POLYMORPHIC
What is a MHC Haplotype
group of MHC alleles linked together on a single chromosome
Define Exogenous and what MHC class are they related too
captured from outside e.g. via phagocytosis
Exogenous antigens are presented via MHC Class II to CD4 T cells
Define Endogenous and what MHC class are they related too
synthesised within cells e.g. virus
Endogenous antigens are presented via MHC Class I to CD8 T cells
Name 3 Antigen presenting cells and their locations
Dendritic Cells
Widely spread
e.g. skin & mucosal tissue
B cells
Lymphoid Tissue
Activated Macrophages Lymphoid Tissue
Antigen presentation via MHC Class I
There are viral proteins in the cytoplasm
Viral proteins are processed - proteasome
The peptides then move into the ER via TAP (transporter associated with antigen processing)
Newly synthesised MHC Class I moves into the ER (it has a signal sequence)
It associates with chaperone proteins which aids its folding
The class I heavy chain binds to the peptide and b2-microglobulin
Once all three are correctly folded, it can go via the golgi to the cell surface for possible recognition by CD8 positive T lymphocytes
Antigen presentation via MHC Class II (exogenous)
Proteins are endocytosed and processed into peptides in endocytic vesicles
The class II molecules get into the ER (as they have signal sequences)
Once in the ER it associates with INVARIANT CHAIN
Invariant Chain - stops peptides that need to be loaded onto MHC Class I from being loaded onto Class II. It also has a targeting signal sequence so the molecules go to the endocytic pathway via golgi
Once they enter the endocytic pathway, the invariant chain is digested away
You end up with a small peptide fragment derived from the invariant chain bound to the MHC Class II known as the CLIP peptide (Class II Associated Invariant Chain Peptide)
Last Step - swapping the CLIP peptide for the antigenic peptide
The antigenic peptide is then loaded onto MHC Class II and moves to the cell surface for recognition by CD4 T lymphocytes
