Lecture 14 - Linking Innate & Adaptive Immunity (MHC and Coreceptors) Flashcards
What can be referred to as a transmembrane glycoprotein that presents antigenic peptides to T-cells?
MHC
What is each chain of the MHC composed of?
Each chain of the MHC has several Ig-like domains - a modular secondary structure shared among many molecules of the immune system.
Once assembled into its quaternary structure, what can be said about MHC? (What structural “features” does MHC have?)
It will posses an allele-specific Ag peptide-binding cleft or groove facing out and a more conserved area facing the cell membrane.
True or False?:
The peptide-binding groove of MHCI is mostly composed of α helices while the peptide-binding groove is mostly composed of β sheets.
False
The peptide-binding grooves of MHCI and MHCII are composed of both α helices and β sheets.
True or False?:
Disulfide bonds are important in the structure of MHC molecules.
True
MHCI can bind peptides of what size?
MHCI can bind short peptides of 8-10 amino acids by both ends.
MHCII can bind peptides of what size?
The length of the peptides bound by MHCII molecules is not constrained.
Where does the peptide exist in the pMHC-TCR interaction?
The peptide is “sandwiched” between the MHC and the TCR.
The interaction depicted in this figure is between an APC and which type of T-cell? How do you know this? (Note: MHC at bottom, peptide in yellow, TCR on top.)
This is a CD8+ T-cell. You can tell because the MHC on the bottom has 3 α subunits (and both subunits interacting with the peptide are α.
True or False?:
A given TCR will bind both to a peptide and the MHC presenting it.
True
Which cell types are professional APCs?
DCs, Macrophages, and Activated B-Cells
Which cell types are non-professional APCs?
All Nucleated Cells in the Body
What is the difference between professional APCs and non-professional APCs?
Professional APCs express MHCI and MHCII molecules and express costimulatory molecules when activated while non-professional APCs express MHCI under normal conditions and do not express costimulatory molecules.
True or False?:
MHCI molecules bind and present peptides generated within the cell (including self proteins) while MHCII molecules bind and present peptides of extracellular origin.
True
Where can MHCII be found?
APCs and Thymus Epithelium
When and how is MHCII expression induced on some cell types that do not normally express MHCII?
During inflammatory resposnes, some cytokines (like IFN-γ) may induce expression of MHCII on some other cell types (like epithelial cells of a given organ).
Why do all nucleated cells express MHCI? What purpose does this have in an immune response?
Self cells express self-peptide that is presented by MHCI to immune cells to present deletion of any self-reactive cells. As well, this self-peptide boudn to MHCI provides an inhibitory signal to NK cells so that they don’t kill them.
Why do T-cells need coreceptors?
T-cells need coreceptors because the TCR-pMHC interaction is a rather low affinity interaction.
CD4 and CD8 are both types of what?
T-Cell Coreceptors
What are the most expressed and least expressed types of T-cell coreceptor (including percentage of T-cells expressing them)?
CD4 is the most expressed (60-70%) type of coreceptor while CD8 is the least expressed (30-40%) type of coreceptor.
What do CD4 and CD8 coreceptors bind to?
CD4 and CD8 bind directly to their associated MHC molecules.
True or False?:
There is a general correlation of T-cell coreceptor and function. CD4+ T-cells have a ‘cytotoxic’ function while CD8+ T-cells have a ‘helper’ function.
False
There is a general correlation of T-cell coreceptor and function. CD4+ T-cells have a ‘helper’ function while CD8+ T-cells have a ‘cytotoxic’ function.
What is the structure of a CD4 coreceptor?
A CD4 coreceptor consists of a single transmembrane protein with four Ig-like domains.
What is the structure of a CD8 coreceptor?
A CD8 coreceptor is a heterodimer linked by a disulphide bond. Each of the transmembrane chains have one Ig-like domain.
What is the function of the CD4 and CD8 coreceptors?
The CD4 and CD8 coreceptors are responsible for binding MHC and enhancing the affinity of the TCR-pMHC interaction along with initating signaling from the TCR.
Which APC signal are the CD4 and CD8 coreceptors involved in?
Activation (Signal 1)
