7 Anitgen recognition by T cells Flashcards
what are T cells
WBC
what do T cells do
play a central role in cell-mediated immunity
how are lymphocytes distinguished
can be distinguished from other lymphocytes (B cells), by the presence of a T-cell receptor (TCR) on the cell surface
what does a T cell receptor look like
very similar to antibody molecule
T cell receptor structure almost identical to one arm of antibody, and always transmembrane
what do T cells recognise
recognise epitopes presented by Antigen Presenting Cells (APC) bearing an MHC molecule, but cannot recognise the peptide alone
what do T cell require
requires breakdown of antigens
what do immunoglobulins
recognises epitopes on molecules in the blood or lymph or on surface of a pathogen
what is TCR for
ONLY for antigen recognition - then sends signal to T-cell
what type of molecule is immunoglobulin
effector molecule
what is MHC
antigen recognition molecule
what does MHC encode
Large number of genes which encode class I and class II molecules (called antigen presenting molecules) + associated molecules
what are MHC evolved for
for antigen presentation to T-cells
what does MHC class 1 present to
CD8+ cytotoxic cells
what does MHC class 2 present to
CD4+ helper cells
what are cytotoxic cells function
kill virally infected cells
- MHC is on every cell of our body (as every cell could be infected by a virus)
MHC class 1 structure
Only 1 alpha chain, with transmembrane region (3 domains)
Peptide binding cleft is part of that alpha chain
Beta 2 microglobulin is a separate molecule which stabilizes structure
MHC class 2 structure
Difference is that there are 2 molecules that form cleft
- Beta peptide and an alpha peptide
how do T cells recognise peptides
T-Cell receptor binds to peptides when they are presented on the surface of the Antigen Presenting Cell – monospecific
what molecules are monospecific
T cells
what molecules are polyspecific
MHC
what is polyspecific
able to have many peptides bind, can present many peptides in there
what are the classes of MHC class 1
3 class I α (A,B and C)
what are the pairs of MHC class 2
3 pairs of Class II α and β (DR, DP, and DQ) but can end up with 4 class II groups (in DR can have alpha was beta I or alpha with beta II)
what is polygenic
there are several different genes for class I and II
what is polymorphic
many alleles for each gene-one of the most polymorphic genes known
MANY peptides can be presented to T-cell
how many of each MHC class does an individual present
Each individual will present 3 sets of class I molecules and 4 class II
which MHC are polymorphic
All MHC products polymorphic except DR-α-reason unknown
what will a typical human express - MHC
6 different Class I molecules
8 different Class II
For class II α and β chains can combine from different chromosomes
what is gene conversion
misalignment in meiosis means copied from a different allele
what is gene recombination
Exchange of DNA segments from different chromosomes
what is the effects of polymorphism
Variability of peptide expression-allows many thousands of sequences to be presented
Rare that a protein has no peptide that can be bound by MHC
BOTH peptide MHC complex is recognised by TCR
where is the variation between MHC allotypes concentrated
- peptide binding groove where they affect peptide recognition
- alpha helices forming walls where affect TCR recognition
peptide specificity
Alleles of MHC confer some specificity on the peptide bound
where is peptide specificity
2-3 residues that form the ANCHOR sequence
length of class 1
only 8-10aa long
length of class 2
variable length
Class I and II present Ag to different cell types
This is achieved by molecular interactions between the CD4 and CD8 glycoproteins and their respective MHC molecules
what are MHC class 1 and 2 known as
coreceptors
what do CD4 and CD8 do
- Stabilise/strengthen TCR/MHC interaction
- Transduce signal to T cell
affinity of TCR
Affinity of TCR is weak-needs other interactions to strengthen binding
cytokine effect on MHC expression
Cytokines increase the expression of MHC molecules-particularly IFN gamma
MHC class 1 expression meaning
Class 1 indicates cell is infected by a pathogen so any nucleated cell can express it, make lots of MHC = to be killed
MHC class 2 expression meaning
Class II presents peptides to T helper cells so tends to be expressed by professional APCs-macrophages, dendritic cells and B cells
How do Peptides get into MHC class 1 molecules
Class I binds molecules come from intracellular viruses and bacteria
How do Peptides get into MHC class 2 molecules
Class II can come from intracellular pathogens OR from an extra-cellular source
what do MHC have to have when no infection
MHC molecules-HAVE to have a peptide bound in absence of infection-may be self
what is the cell divided into 2 compartments
1 Nucleus and cytosol – intracellular
2 Vesicular system (secretory part) -ER, golgi, endocytic vesicles
what is the cell in contact with
extracellular fluid
what expresses peptides
- Class I are endogenous-intracellular
- Class II exogenous-extracellular
where are class 1 degraded
cytocol
where are class 2 degraded
endocytic vesicles
mononuclear phagocytes and antigen presentation
phagocytosis, present fragment
B cell and antigen presentation
B cells brought through surface Ig
dendritic cells and antigen presentation
brought through by pinocytosis
Class II and extracellular molecule movement
Class II translocated to ER on way to surface
what is done to prevent premature binding of peptides and effect
To prevent premature binding of other peptides the invariant chain binds (also on MHC)
also helps MHC get to the low pH endosome where proteins are degraded
MHC and endosome fuse, invariant chain cleaved and replaced by peptide
why is HLA DM important
needed for T cell activation
what is required for MHC class 1
Intracellular peptides require processing
where are the antigen processing genes for class 1
in the MHC
what is located in the MHC locus
LMP
TAP
what forms a proteosome
two LMP units
what does the proteosome do
continuously degrades proteins to peptides-from the cytosol including those from pathogens
what is proteosome expression induced by
IFN
what do TAP 1 and 2 form
complex that selects the peptides that can be transported into the ER
where are peptides made
cytosol
where are peptides transported
ER
