TCR and MHC Flashcards
Why do T cells have to be present at the site of antigen, but B cells don;t?
Because T cells can’t secrete their receptors while B cells can (antibodies)
When do Th0 cells decide what type of Th to become?
When the correct antigen is brought to them by dendritic cells
What’s the main determinant of the precursor T cell’s ultimate progeny?
It all depends on what the dendritic cell experienced - where they were activated, what TLR was used, what cytokines were involved, etc.
What two cytokines will induce formation of Th1 cells?
IL-12 and IFN-alpha
What important lymphokine is secreted by the Th1 cells which acts as a pro0inflammatory and a chemotatic agent for monocytes?
interferon gamma
Monocytes that are activated by interferon gamma become what?
classically activated M1 (angry) macrophages - they ingest and kill bacteria
Classically activated M1 macrophages then secrete what two cytokines which intensity inflammation locally?
TNF alpha and IL-1
Why are Th17 cells called that?
They secrete IL-17 as a cytokine (among others)
What cytokines will induce formation ot Th17 cells?
TGF-beta and IL-21
Like Th1 cells, Th2 cells will secrete cytokines to attract and activate macrophages, but in a different way. how? with what cytokines?
Using IL-4 and IL-13, they alternatively activate the macrophages = M2. They’re more involved in healing
IL-4 is chemotactic for macrophages and what other WBC?
Eosinophils
Th2 cells will also give rise to what other type of T helper cells?
Th2-like follicular cells, which migrate into lymphoid follicles
The high levels of IL-4 secreted by the TH2-like follicular cells will cause B cells to do what Ig class switch?
from IgM/IgD to IgE
In more general terms, what do the follicular helper T cells do?
They help the B cells become activated and differentiate into plasma cells
WHat do T regulatory cells do?
They’re anti-helpers - they secrete cytokines to inhibit all the other helper cells
What cytokines do the Treg cells produce?
TGF-beta and IL-10
What are the two ways cytotoxic T cells can kill a cell?
Either way, it binds with Fas on the Fas ligand (CD95 and CD95L)
- cross-linked Fas triggers a latent apoptosis pathway
- secrete lytic granules with granzymes and perforins
What cytokine from the Th1 cells is necessary for T cells to become active cytotoxic T cells?
IL-2
What surface markers do we use to distinguish B cells?
CD19 and CD20
WHat surface markers do we use to distinguish T cells?
CD3 (they all have), CD4 and CD8
What does “MHC-restriction” mean?
T cells are restricted in their recognition to antigen on the surface of cells that have GENETICALLY IDENTICAL MHC molecules as themselves - so my T cells won’t kill one of Chris’s infected cells
How do dendritic cells present things on MHC?
The antigen enters the dendritic cell and is broken down to peptides in the endosome.
the endosome fuses with other vesicles that have MHC molecules facing inwards.
Some of the peptides will bind to the MHC molecules
THe bound MHC molecules are recycled back to the surface
Can T cells recognize free antigen?
nope - it’s gotta be on MHC
What are the two types of MHC molecules and on what cells are they usually located?
type 1 and type 2
type 1 are on all nucleated cells, type 2 are on phagocytes and B cells
Which MHC class presents antigens endocytosed by a cell? Which MHC class presents antigens synthesized by a cell?
MHC 1 - synthesized
MHC 2 - endocytosed
Why are dendritic cells capable to rpesenting to both Cd4 and Cd8 T cells?
They are able to undergo “cross presentation” because they can leak some of its antigen over to it’s intrinsic pathway so it will present them on class 1 and class 2 at the same time
Why are dendritic cells considered to be more effective at presenting than macrophages and B cells?
- dendritic cells constitutively express both MHC and costimulatory molecules
- macrophages must first be activated to express both MHC molecules and costimulatory molecules
- B cells will constitutively express MHC 2 molecules, but need to be active to express costimulatory molecules
Describe the structure of a T cell receptor.
2 chains; alpha and beta OR gamma and delta
each chain has a variable region and a constant region
it’s always membrane bound in the form of a heterodimer
Which to T cell receptors undergo: somatic mutation of somatic hypermutation?
only somatic mutation - because T cells that have left the thymus are no longer under any sort of regulation, so if they changed once they left there would be no shutting them off
What CD molecule is closely associated with the TCR? What does it do?
CD3 - it transduces TCR signals for the T cell when the TCR binds the appropriate MHC
Why are co-receptors necessary for the TCR/MHC interactions?
Because without them the binding is relatively weak
There are other co-receptors that add to the binding affinity besides CD4 and CD8, such as…
CD2 binds to LFA-3
LFA-1 binds to ICAM-1
CD28 binds to B7
CD45R binds to CD22
What gene segments are present in the alpha chains and beta chains of the TCR? Hint - it’s similar to Ig…
alpha: made up of V, J, and constant segments
beta: made up of V, D, J, and constant segments
What enzyme complex does the gene rearrangement for the TCR?
RAG recombinase again
The TCR has an addition strategy for increased diversity that Igs do not, which is…
alternative joining of the D sequences to give VJ, VDJ, or VDDJ chains
Why would it be a bad idea to allow somatic hypermutation in T cells?
It could lead to autoimmunity because we wouldn’t have a mechanism to get rid of them
T cells will produce a single beta chain, but can produce two different alpha chains (one from dad and one from mom), so why do functional T cells only express specificity for one antigen?
Because in order to exit the thymus, they have to 1. recognize self MHC and be 2. self tolerant and 3. not recognize free antigen
So it’s highly unlikely that even one receptor will pass this inspection, let alone two on one cell.
Describe the genetics related to MHC Class 1. How many loci? What additional peptide do all the gene products combine with for class 1? So how many are possible within an individual?
There are three classical Class 1 gene loci: gene A, B, and C (encoding HLA-A, HLA-B, and HLA-C)
They all combine with another peptide called Beta2 microglobulin
For each of the loci, you inherit one allele from mom and one from dad, so in total an individual can make 6 different MHC Class 1 molecules
Describe the genetics related to MHC Class 2. How many loci? What do they combine with? So how many are possible within an individual?
There are three major genes loci again, but each gene locus encodes TWO peptides which can mix and match - an alpha and a beta subunit - to be expressed on the surface
Gene DP encodes DP alpha beta
Gene DQ encodes DQ alpha beta
Gene DR encodes DR alpha beta
Since you inherit one allele from mom and one from dad, there are 12 possible MHC class 2 molecules in an indiivdual
There are TONS of polymorphisms for the MHC molecules. Where are most of them located within the molecule?
in the cleft region - the antigenic binding site
MHC class 1 molecules tend to bind ____ peptides and have an end-___ conformation.
MHC class 2 molecules tend to bind ____ peptides and have an end-___ conformation
1: shorter peptides, end-closed conformaton
2: longer peptides, end-open conformation
