Lecture 14 - Linking Innate & Adaptive Immunity (MHC and Coreceptors)

Question 1

What can be referred to as a transmembrane glycoprotein that presents antigenic peptides to T-cells?

Answer 1

MHC

Question 2

What is each chain of the MHC composed of?

Answer 2

Each chain of the MHC has several Ig-like domains - a modular secondary structure shared among many molecules of the immune system.

Question 3

Once assembled into its quaternary structure, what can be said about MHC? (What structural “features” does MHC have?)

Answer 3

It will posses an allele-specific Ag peptide-binding cleft or groove facing out and a more conserved area facing the cell membrane.

Question 4

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.

Answer 4

False

The peptide-binding grooves of MHCI and MHCII are composed of both α helices and β sheets.

Question 5

True or False?:

Disulfide bonds are important in the structure of MHC molecules.

Answer 5

True

Question 6

MHCI can bind peptides of what size?

Answer 6

MHCI can bind short peptides of 8-10 amino acids by both ends.

Question 7

MHCII can bind peptides of what size?

Answer 7

The length of the peptides bound by MHCII molecules is not constrained.

Question 8

Where does the peptide exist in the pMHC-TCR interaction?

Answer 8

The peptide is “sandwiched” between the MHC and the TCR.

Question 9

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.)

Answer 9

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.

Question 10

True or False?:

A given TCR will bind both to a peptide and the MHC presenting it.

Answer 10

True

Question 11

Which cell types are professional APCs?

Answer 11

DCs, Macrophages, and Activated B-Cells

Question 12

Which cell types are non-professional APCs?

Answer 12

All Nucleated Cells in the Body

Question 13

What is the difference between professional APCs and non-professional APCs?

Answer 13

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.

Question 14

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.

Answer 14

True

Question 15

Where can MHCII be found?

Answer 15

APCs and Thymus Epithelium

Question 16

When and how is MHCII expression induced on some cell types that do not normally express MHCII?

Answer 16

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).

Question 17

Why do all nucleated cells express MHCI? What purpose does this have in an immune response?

Answer 17

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.

Question 18

Why do T-cells need coreceptors?

Answer 18

T-cells need coreceptors because the TCR-pMHC interaction is a rather low affinity interaction.

Question 19

CD4 and CD8 are both types of what?

Answer 19

T-Cell Coreceptors

Question 20

What are the most expressed and least expressed types of T-cell coreceptor (including percentage of T-cells expressing them)?

Answer 20

CD4 is the most expressed (60-70%) type of coreceptor while CD8 is the least expressed (30-40%) type of coreceptor.

Question 21

What do CD4 and CD8 coreceptors bind to?

Answer 21

CD4 and CD8 bind directly to their associated MHC molecules.

Question 22

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.

Answer 22

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.

Question 23

What is the structure of a CD4 coreceptor?

Answer 23

A CD4 coreceptor consists of a single transmembrane protein with four Ig-like domains.

Question 24

What is the structure of a CD8 coreceptor?

Answer 24

A CD8 coreceptor is a heterodimer linked by a disulphide bond. Each of the transmembrane chains have one Ig-like domain.

Question 25

What is the function of the CD4 and CD8 coreceptors?

Answer 25

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.

Question 26

Which APC signal are the CD4 and CD8 coreceptors involved in?

Answer 26

Activation (Signal 1)