Immune responses to glycolipids and polysaccharides

Question 1

What kind of antigens does CD-1 recognize?

Answer 1

Lipids.

Question 2

Which CD1 isoforms belong to which groups?

Answer 2

CD1a,b and c belong to group I, CD1d to group II and CD1e to group III

Question 3

Where are group I CD1s expressed?

Answer 3

Thymocytes and Dendritic Cells.

Question 4

Where is CD1d expressed?

Answer 4

B-cells, monocytes, DCs and Activated T-cells

Question 5

What does CD1e do?

Answer 5

It does not play a role in antigen presentation, it plays a role as a lipid transfer protein in Dendritic Cells.

Question 6

What is the striking difference between CD1 and MHC-I?

Answer 6

CD1 has a binding pocket that can bind hydrophobic parts of a protein and exposes the polar side of the molecule exposed for TCR recognition.

Question 7

Which CD1 has the smallest groove and which CD1 has the biggest groove?

Answer 7

CD1a has the smallest groove and CD1b has the biggest groove, with more than A’ and F’ binding sites.

Question 8

What is beta-2 microglobulin?

Answer 8

The transmembrane part of a CD1 protein.

Question 9

Which ER protein plays a pivotal role in the assembly of CD1?

Answer 9

microsomal triglyceride transfer protein (MTP)

Question 10

What is the function of MTP?

Answer 10

lipid antigen loading on CD1 in the ER

Question 11

Briefly explain the surface expression and loading of CD1 molecules.

Answer 11

The CD1 molecules are being made in the ER where they travel to the Golgi system. There they are glycosylated and expressed on the cellular surface. Then they are transported into endosomes, where most lipid antigen loading happens. Different lipids are being loaded at different stages (Early endo, late endo and lyso)

Question 12

Why are lipids transported and processed using LTPs?

Answer 12

Because they are hydrophobic. they need to be transported through designated vesicles and interact using receptors.

Question 13

What happens to endogenous and exogenous lipids in the context of loading onto CD1?

Answer 13

In endocytic compartments, LTPs assist binding of lipids to CD1. Some self-lipids are loaded onto CD1 during their folding in the ER. Exogenous lipids need to be loaded from membranes or lipid-protein complexes.

Question 14

Name some proteins which facilitate loading of lipids on CD1

Answer 14

Saposins, GM2 activator, NPC2 and CD1e

Question 15

Which proteins cannot remove lipids from CD1 once they are loaded?

Answer 15

Saposins.

Question 16

On what CD1 does CD1e facilitate the loading of lipids?

Answer 16

promotes loading of CD1d and influences lipid presentation of CD1b and CD1c

Question 17

What other element, besides LTP, leads to the loading of lipids on CD1?

Answer 17

The low pH that is present in the endosomes. This element relaxes the protein, allowing chains to bind inside it.

Question 18

How are CD1d-restricted T-cells called?

Answer 18

Natural Killer T-cell, which expresses both NK and T-cell surface markers and can bind to a variety of lipids.

Question 19

What is the difference between group I CD1-restricted T-cells and Group II CD1-restricted T-cells?

Answer 19

Group I acts in a more adaptive way and arises later in an immune reaction while Group II acts somewhere in between adaptive and innate.

Question 20

What helper function do activated group I CD1s resemble and what cytokines do they produce?

Answer 20

They resemble Th0 and Th1 functions and produce IFNy and TNFa.

Question 21

Which CD1 cells are some of the most common self-reactive CD1s? Where are they common?

Answer 21

CD1a. they are common in the skin and peripheral blood.

Question 22

What is alpha-GalCer?

Answer 22

The lipid antigen that has the strongest immunity out of all lipids known on earth (so far).

Question 23

What is special about iNKT (Type I NKT)?

Answer 23

They can produce high amounts of cytokines either through a TCR dependent or independent manner.

Question 24

Does the CD8 marker arise on Type I or Type II CD1 T-cells?

Answer 24

It arises on Type II CD1-T-cells (Type II NKT)