Antigen Presentation and the MHC

Question 1

List the different types of Ag presenting cells

Answer 1

Macrophages
Dendritic cells
B lymphocytes

Question 2

What are the signals required to activate T lymphocytes?

Answer 2

f

Question 3

What is special about Ag presenting cells in regard to MHC?

Answer 3

Cells that present Ag in context of an MHC class II molecule are called Ag presenting cells, even though all cells express and can present Ag via MHC class I molecules

Question 4

Where are macrophages found? Are they phagocytic?

Answer 4

Blood, liver, spleen

they are phagocytic

Question 5

Where are dendritic cells found? Are they phagocytic?

Answer 5

Skin, lymphoid tissue

They are phagocytic

Question 6

Where are B cells found? Are they phagocytic?

Answer 6

Lymphoid tissues, sites of immune reactions

They are not phagocytic

Question 7

What are mononuclear phagocytic cells localized in tissue called? What are some tissue specific names of these?

Answer 7

Macrophages

Macrophages in the brain are microglial cells

Macrophages in the liver are Kupffer cells

Question 8

What is the function of macrophages?

Answer 8

phagocytosis and activation of bactericidal mechanisms

Ag presentation

Question 9

What are the different sub-types of tissue specific dendritic cells?

Answer 9

Skin: Langerhans’ cells, present to T lymphocytes

T-lymphocyte area of lymph node: interdigitating dendritic cells

B-lymphocyte area of lymph node: follicular dendritic cells

Question 10

What is the function of Dendritic cells, and where/to whom do they present Ag?

Answer 10

Ag uptake in peripheral sites, Ag presentation in lymph nodes

Found in B lymphocyte areas of the lymph node and spleen - present to B lymphocytes

Question 11

What are the two lineages of dendritic cells?

Answer 11

conventional: undergo maturation
plasmocytoid: release IF in response to viral infections

Question 12

during which response is B cell presentation most important?

Answer 12

The secondary response

Question 13

What compartments does Ag and MHC processing take place in for class I and II?

Answer 13

Cytoplasmic processing is associated with MHC class I

Endosomal processing is associated with MHC class II

Question 14

From what are Ag peptides that bind to MHC class I typically derived?

Answer 14

From viruses that take over cellular machinery and produce viral protein

Can also be from defective proteins (DRiPs - defective ribosomal products)

Question 15

How are viral proteins/DRiPs degraded by the cell?

Answer 15

via proteosomes (LMP2 and LMP7)

Question 16

What occurs after degradation of protein into peptides?

Answer 16

The viral peptides are transported into the ER via TAP1 and TAP2, where they are further trimmed by ERAAP

Question 17

What are the chaperone proteins that help assemble the MHC class I molecule in the ER?

Answer 17

Calnexin: binds alpha chain until beta2 microglobulin binds

Erp57, Calreticulin

Question 18

What does the MHC-I/Erp57/Calreticulin complex do next?

Answer 18

It binds to TAP via Tapasin, and accepts peptide

Question 19

From what are Ag peptides that bind to MHC class II typically derived?

Answer 19

From Ag captured and internalized by specialized APCs

Question 20

Where are peptides that bind to MHC class II generated?

Answer 20

in acidified endosomes that fuse with vesicles containing MHC class II

Question 21

How are MHC Class II molecules transported from the ER?

Answer 21

MHC-II molecules are synthesized in the ER and are transported with a chaperone moleule, Ii (invariant chain) that blocks binding of peptide in the active site

Question 22

How is Ii degraded?

Answer 22

Acidification of the vesicle degrades the invariant chain, but leaves a small portion (CLIP) in the binding site

Question 23

How is CLIP released?

Answer 23

After fusion of the vesicle carrying the MHCII molecule with an endosome carrying peptide, the protein loader/unloader HLA-DM removes CLIP

Question 24

How does MHCII sample peptide?

Answer 24

HLA-DM will repeatedly place different peptides into the MHCII binding groove until one fits with high affinity

Question 25

What do MHCI and MHCII bind under normal (non-pathogenic conditions?)

Answer 25

MHCI binds self-peptide, MHCII binds CLIP

Question 26

What do CD4+ T lymphocytes recognize?

Answer 26

They do not recognize free/soluble Ag! They recognize Ag presented by APCs in the context of MHCII

Question 27

How does an APC determine the fate of a T cell?

Answer 27

The T cell is restricted by the MHCII molecule on which the Ag was recognized: Antigenic restriction

Question 28

What is the response of CD4+ T cells?

Answer 28

Can either mediate phagocyte activation or act as helper cells by releasing cytokine

Question 29

What are the subtypes of CD4+ cells, and what are their main functions?

Answer 29

Th1: Produce cytokines that activate macrophages Th2: produce IL that results in the proliferation of B cells to induce Ab synthesis

Question 30

Activation of a naive T cell by Ag requires what two signals?

Answer 30

Ag presentation via MHCII Interaction between B7 on the APC and CD28 on the T cell

Question 31

APCs that have taken up Ag that is not a microorganism, do not always express B7. In this case, how do they activate T cells?

Answer 31

T cells that recognize Ag in context of MHCII on an APC will express CD40L, which engages CD40 on the APC. This stimulates the APC to produce B7, which can activate the T cell via CD28 on the T cell

Question 32

B cells that have taken up Ag often require both B cells and T cells. How does this interaction lead to the production of Ab?

Answer 32

B cells take up Ag and present it via MHCII, which also stimulates the B cell to produce B7. MHCII interaction with a TCR and B7 interaction with CD28 will co-stimulate the T cell to produce CD40L. CD40L engages CD40 on the B cell, which stimulates the B cell to produce cytokine receptors, and stimulates the T cell to release cytokines necessary for the proliferation of the B cell. The B cell binds the cytokines, resulting in proliferation into an Ab secreting plasma cell.

Question 33

Define the mature immunological synapse

Answer 33

a specific pattern of receptor segregation, with a central cluster of TCRs/CD4/CD28 that are important in signaling surrounded by a ring of adhesion molecules, such as LFA-1 (aka CD11a, T cells) interacting with I-CAM1 (on the APC)

Question 34

What is the co-stimulatory molecule expressed on CD4+ T lymphocytes?

Answer 34

CD28

Question 35

What type of Ag do B cells present?

Answer 35

Only the Ag to which the B cell receptor is specific

Question 36

How is B cell recognition of Ag different from other APCs?

Answer 36

MHCI: Viral (cytoplasmic protein) MHCII: endocytosis of foreign material B cells: bind Ag on BCR, endocytose (they are NOT phagocytic), load into MHCII

Question 37

What is the inhibiter of DM?

Answer 37

DO

Question 38

What are the different genes and their products that are included in the HLA Class II gene?

Answer 38

DP, DQ, DR - MHCII molecule LMP (2 and 7) - proteasome TAP - TAP TAPBP - Tapasin DO(A/B) - inhibitor of DM DM - peptide loader