8 - Adapt 2: Innate-Adaptive (T Cell) Interaction Flashcards
Antigen recognition and T Cell development
CD4 T-cells are also known as ______ T-cells and have MHC ___
Helper; 2
CD8 T-cells are also known as ______ T-cells and have MHC ___
Cytotoxic; 1
What do T-cells use T-cell receptors (TCR’s) for?
To help them “see” the antigen
CD8 and CD4 are _______
Coreceptors
What is the purpose of having coreceptors?
To stabilize the complex interactions of the TCR
What are the majority of TCR’s composed of?
alpha and beta chains
What is CD3?
A coreceptor on the alpha-beta TCR
What does ITAM stand for?
Immune-mediated Tyrosine-based Activation Motif
What differs on TCR’s that determines which peptide (antigen) it can bind?
Complementarity Determining Region (CDR)
What two structures do TCR’s associate with that help propagate signals?
CD3 (coreceptor) and zeta chains
How can TCR’s recognize so much diversity in antigens?
Different CDR’s!
What is a T-cell receptor gene?
T-cell receptor protein that can recognize virtually all the potential AA sequences in a peptide
What is the big problem with the TCR gene?
The genome is too small to encode all the genes needed to code for the diversity of antigens
What are the two theories about how TCR diversity is generated?
-Modified germ-line theory
-Somatic hypermutation theory
Which TCR diversity theory is likely to be true?
Both!
Each TCR molecule is encoded by multiple, germ-line, variable-region gene segments, which are rearranged differently and randomly in each naive immune cell to produce a diverse primary receptor repertoire (done pre-birth)
What are the 4 segments in TCR genes?
-Variable (V)
-Diversity (D)
-Joining (J)
-Constant (C)
Which segments does the alpha chain have?
V and J
Which segments does the beta chain have?
V, D, and J
What is VDJ recombination?
Gene recombination that joins random copies of each segment together
Which genes mediate VDJ recombination?
RAG1 and RAG2 (recombination activating genes)
How do RAG1/2 function?
They will randomly bind to a single gene on the alpha or beta chain and then join that with another gene segment and it will bring the two segments together. This will create a hairpin loop that will get spliced out. In the beta chain, this new double segment will then be linked with another segment (because beta is VDJ and alpha is only VJ)
What is TdT?
Terminal Deoxynucleotidyl Transferase. Randomly adds nucleotides to join spliced ends of the alpha/beta chains
What can TdT introduce?
Mutations
What enzyme cleaves out hairpin loops from from the recombined chain?
DNA-dependent protein kinase
Where is the variation in each TCR alpha/beta chain introduced
In CRD3! *Know this cause its highlighted in red twice so probably important
Where does screening of good TCR’s occur?
Thymus stroma, then migrates to thymus medulla (done before birth)
What is -/- selection?
Cell has no CD4 or CD8
What is +/+ selection?
Cell has both CD4 and CD8
What is +/- selection?
Cell has either CD4 or CD8
What happens to T-cells with a non-functional TCR?
Destroyed
What happens to T-cells with a self-reactive TCR
DESTROYED
What happens to T-cells with a non-self reactive TCR
Allowed to live :) goes to periphery
What 2 things occur during T-cell development and what is the result?
-Positive selection of functional T-cells via CD4, CD8 and MHC recognition
-Negative selection of self-reactive T-cells
*Results in naive T-cells (1-4%)
What type of cells is negative selection mediated by?
Macrophages and dendritic cells
How are T-cells positively selected?
The TCR will have a preference for MHC1 or MHC2 and then will just lose expression of the unused CD4 or CD8
What type of cells do developing T-cells bind to during positive selection to recognize an MHC complex?
Epithelial antigen presenting cells (cortical and medullary epithelial cells)
What happens to the beta chain after recombination?
It moves to the surface of the cell and binds the pre-alpha chain, which makes the whole thing a pre-TCR
What does the pre-TCR do?
Tests if the cell can signal, and if it can then it makes the alpha chain and forms a complex with CD3 and zeta chain
What happens if the TCR is bound to MHC1?
Will express CD8, will cease to express CD4
What happens if the TCR is bound to MHC2?
Will express CD4, will cease to express CD8
Do CD4 and CD8 contribute to antigen specificity of the TCR?
NO
What leads to activation of a T-cell via signals transduced through the CD3 complex of molecules?
Combination of TCR and CD4 or CD8 binding
What “educates” T lymphocytes?
Thymocytes. Teaches to differentiate self vs non-self
What is AIRE?
Auto-immune regulator gene
What does AIRE do?
Expresses proteins within the thymus so self-reactive T-cells are negatively selected
Why does a mutation in DNA-dependent phosphokinase (a DNA repair gene) lead to Arabian foals not being able to control infections? What is this disease called?
Called Severe Combined Immunodeficiency Disease (SCID). The mutated gene is responsible for re-ligation of cut DNA, so it can’t make functional TCR’s.
