Flashcards in 10 T cell receptor activation Deck (42):
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.
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?
where do the majority of peptides come from that are presented on MHC 1 come from?
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?
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
T/F MHC class 1 genes have higher numbers of alleles because they encode the entire peptide cleft?
which class of MHC (1 or 2) has higher diversity?
Class 2. Although class 1 has a larger number of alleles, the class 2 molecules undergo random recombination of the alpha and beta genes.
what are the 3 classes of type 1 MHC? Type 2?
Type 1 = A,B,C
Type 2 = DP, DQ, DR
T/F Class 1 and class 2 MHC are both polymorphic and polygenic?
Polymorphic= having multiple alleles for the same gene.
Polygenic= having multiple genes with the same function.
what allows for MHC 1 and 2 to have so much diversity?
different inherited combinations of alleles at the MHC genes. We can have up to 16 different combinations from parents.
what is a haplotype? what does it mean when the MHC locus in inherited as a haplotype?
1) Haplotype: the particular combination of MHC alleles on a single chromosome (linked groups of 3)
2) It means that these combinations (haplotype) are inherited as if they were a singe gene.
where do you find the majority of diversity of the MHC classes?
in the peptide binding clefts
specific haplotypes of MHC class II have been linked to the pathogenesis of what?
T/F If i have a know pathogenic haplotype, I will end up with a disease?
false, the presence of a pathogenic haplotype does not cause the disease, but increases susceptibility.
what frequently causes transplant rejection?
peptides from the donor as antigen. Host T cells recognize the MHC from the donor and attack the graft.
which type of cell generally tries to reject the new organ transplant?
CD8 T cells because they are looking for the incorrect MHC class 1 which are on every cell.
which types of transplants match MHC compatibility?
kidney and bone marrow mainly.
What is type 2 bare lymphocyte disease?
when there are defects in the transcription factors needed for MHC II expression. This means that you cant activate any CD4 cells.
These patients have reduced CD4 cells and die by the age of 10 by an infection.
what is type 1 bare lymphocyte disease?
when there is a defect in the expression of TAP1, TAP2, or Tapasin.
The patients develop a sensitivity to bacteria and parasites, but usually dies from respiratory insufficiency.
how does a superantigen work to kill the host?
it activates both the MHC and the TCR in very large quantities with cytokine release causing it to be overwhelmed. This eventually leads to immune suppression and vulnerability to the pathogen.
T/F bacteria, mycoplasms, and viruses can all produce superantigens?
viruses can block proper function of MHC class 1. why do they usually mess up class 1 and not 2?
because they are intracellular pathogens and they want to live.
They can block TAP, Compete with taposin, or even ubiquinate the MHC complex for distruction.