10 T cell receptor activation Flashcards
what is the key cell type that activates the CD4 and CD8 cells? How does it do it?
Key cell= dendritic cell
It uses MHC 2 or MHC1 bound to an antigen to activate it.
T/F Each TCR recognizes one or a small number of antigens presented by the MHC complex.
True
The TCR interacts with both the antigen and the MHC.
How many TCR/MHC interactions are required to activate the T cell? How many TCR’s are generally on a T cell?
10-20 TCR’s are sufficient to activate a T-cell
There can be up to one hundred thousand receptors on each cell.
CD8 binds to? CD4 binds to?
CD8=MHC1
CD4=MHC2
where do the majority of peptides come from that are presented on MHC 1 come from?
intracellularly.
The exception is with dendritic cells that can present MHC 1 with extracellular antigen.
which 2 components make up the MHC 1 complex?
alpha(1-3), and beta 2 microglobulin
what is the function on beta 2 microglobulin on the MHC 1 complex?
- stabilizes the complex
- promote release from calnexin
MHC 1 binds peptides that are which length?
8-10 amino acids long.
which part of the MHC class 1 binds the antigen?
The alpha subunits
where is MHC class 1 produced?
In the E.R.
Know order of MHC class 1 pathway to surface.
1) (E.R bound) Pre-MHC 1 bound to Calnexin.
2) Beta 2 microglobulin binds MHC 1 displacing Calnexin.
3) MHC 1 binds to calreticulin, ERp57, & Tapasin
4) Proteases degrade intracellular peptides
5) Fragmented peptides passed through TAP into the lumen of ER
6) ERAAP binds peptide fragments in ER lumen, shaves to correct size, and places on MHC 1.
7) MHC releases form all attaching proteins, and exported to cell membrane.
where do the peptides come from that are being presented on MHC class 1 molecules?
1) cytosolic proteins. (ex. normal or viral)
2) defective proteins
3) Retrotranslated proteins from ER
Note: dendritic cells can also place endocytosed proteins in cytosol and endocytosed proteins from recycled MHC 1
what is cross presentation?
The mechanism used by dendritic cells to load extracellular proteins onto MHC class 1.
why is cross presentation critical?
it is necessary for the ability of dendritic cells to activate naive CD 8 T-cells. In order for dendritic cells to do this, they first need to be activated by CD4 T- cells. (this is called licensing)
what is “Licensing”?
The activation of dendritic cells by CD 4 T cells is called licensing.
How do exogenous proteins get into the cell to become expressed on MHC class 1?
The proteins are phagocytosed, and transported to the cytosol by Sec61 complex. From there they are degraded by a proteosome and loaded onto MHC class 1 through the normal pattern.
what makes up the MHC class 2?
alpha and beta chains.
which part of the MHC 2 binds the antigen?
both alpha and beta.
how long are the chains that MHC 2 binds?
12-20 amino acids.
where do you generally find MHC class 1 molecules? what about class 2?
class one= every nucleated cell in the body class two= on antigen presenting cells (macrophages, B-cells, and dendritic cells)
What is the process to get the antigen onto MHC 2?
1) MHC bound to invariant chain in ER lumen.
2) endosome buds off and becomes acidic, causes invariant chain break, clip still blocks active site.
3) Endocytosed antigens are imported and degraded and fuse with MHC 2 endosome.
4) HLA-DM binds to MHC 2 endosome displacing CLIP allowing other peptides to bind.
5) endosome fuses with cell membrane.
where do the antigen presenting cells get the peptides that are to be placed on MHC 2?
phagocytosis
macropinocytosis
autophagy
which receptor is required for eliminating intracellular pathogens? which is required for activating the adaptive immune response to all pathogens?
1) MHC 1 which activates CD8
2) MHC 2 which activates CD4
on which chromosome do you find the MHC locus? how many genes are there?
chromosome 6, and there are 200 genes
