Antigen Presentation

Question 1

CD8 on T cell interacts with ___ domain on MHC I

Answer 1

alpha 3

Question 2

what binds to MHC I?

Answer 2

TCR of Tc cells and CD8

Question 3

T or F. Peptides will bind to closed groove of MHC I

Answer 3

T (8-11 AAs)
anything longer = will not fit
shorter = will but won’t stay very long

Question 4

for MHC Iwhere in the cell are peptides loaded?

Answer 4

endoplasmic reticulum

Question 5

where do peptides come from to be loaded to MHC I?

Answer 5

comes from inside cell (endogenous peptides)

Question 6

where is MHC I located

Answer 6

on all nucleated cells

Question 7

CD4 on T cell interacts with __ and __ domains of MHC II

Answer 7

Beta 2 and alpha 2

Question 8

what are MHC I made of?

Answer 8

heavy chain + B2-microglobulin

Question 9

what are MHC II made of?

Answer 9

alpha and B chains

Question 10

what binds to MHC II

Answer 10

TCR of Th cells and CD4 (helps with anchoring and recognition)

Question 11

where do peptides bind to MHC II?

Answer 11

open ended groove
12-22 AAs

Question 12

where in the cell are peptides loaded on MHC II?

Answer 12

endosomal pathway

Question 13

where do peptides comes from for MHC II?

Answer 13

outside/exogenous peptides

Question 14

which types of cells express MHC II?

Answer 14

professional APCs and cytokine-activated cells
ex: endothelial cells normally are not APCs but when activated by cytokines could become APCs

Question 15

TAP

Answer 15

transporter associated with antigen processing

peptide transport to the rough endoplasmic reticulum

ATP-dependent

2 subunits = TAP1 and TAP2

transports 8-16 peptides

Question 16

Tapasin

Answer 16

tells MHC to move towards TAP = where peptides come in

Question 17

ERAP

Answer 17

breaks down peptides to ensure it is 8-11 AAs long
if correct size = dislodges ERp57

Question 18

the types of antigens that uses exogenous pathway

Answer 18

peptides from internalized bacteria or viruses

internalized self proteins

Question 19

cells that present antigens for exogenous pathway

Answer 19

antigen presenting cells

Question 20

cells that recognize Ag+ MHC II for exogenous pathway:

Answer 20

CD4 + Th cells

Question 21

criteria for APCs

Answer 21

must express MHC II
must be able to deliver a co-stimulatory signal

Question 22

professional APC

Answer 22

dendritic cells = most effective; do majority of naive T cell activation

macrophage = must be activated by phagocytosis

B cells = must be activated by antigen

Question 23

non-professional APC

Answer 23

any cells inducible by interferon (IFNy)
= skin fibroblasts, glial cells, pancreatic beta cells, vascular endothelial cells

Question 24

MHC II peptide loading

Answer 24

alpha and beta chains made in RER

invariant chain immediately binds to MHC II in RER
- helps with MHC II folding - chaperone
- prevents peptides in RER from binding to MHC II
- directs MHC II out of RER to early endosomes

three MHC II complexes combine with 3 invariant chains to form a nonamer

Question 25

bare lymphocyte syndrome type I

Answer 25

• lack surface MHC I
• mutated Tap 1 or 2 = can’t move peptides into RER if can’t load MHC = unstable = will not go to surface
• Tc decreased, normal Th
• do well with viral but not with bacterial infections
• necrotizing skin lesions, respiratoru nacterial infections
• excessive NK cell activation, thymic selection

Question 26

bare lymphocyte syndrome type 2

Answer 26

• lack surface MHC II
• usually due to transcription factor defects
• massive decrease in Th cell activation, normal Tc
• severe combined immunodeficiency
• no help for B cells

Question 27

three characteristics of MHC

Answer 27

• polygenic (multiple genes)
• polymorphic (multiple alleles for each gene)
• co-dominant (paternal and maternal genes are co-expressed)

Question 28

mouse MHC genes

Answer 28

histocompatibility-2 (H2 genes)

Question 29

human MHC genes

Answer 29

human leukocyte antigen (HLA) genes

Question 30

types of antigens used in an endogenous pathway

Answer 30

peptides from replicating viruses

intracellular misfolded self-peptides

Question 31

target cells for endogenous pathway or cells that present these antigens

Answer 31

any nucleated cell expressed MHC I

Question 32

cells that recognize Ag + MHC I

Answer 32

cytotoxic T cells (CTLs = Tc = CD8+ cells)

Question 33

describe the cytosolic processing of antigens

Answer 33

• protein infects cell
• protein ubiquitination
• proteasome breaks down proteins into peptides and eventually AAs
• this is loaded onto MHC I

Question 34

where are immunoproteasomes found?

Answer 34

in all professional APCs and also in the presence of IFNy/TNFa during an infection

Question 35

define immunoproteasomes

Answer 35

special proteases that increase speed and frequency of 8-10 AA peptide formation = binds MHC I

Question 36

describe MHC II peptide loading

Answer 36

MHC II and invariant chain binds

invariant chain is digested and remnant (CLIP) stays with MHC II

HLA-DM catalyzes CLIP exchange with peptide

HLA-DO binds to HLA-DM and negatively regulates activity

Question 37

these are non-classical MHC II

Answer 37

HLA-DM and HLA-DO

Question 38

four mechanisms for uptake of foreign lipids by cells

Answer 38

1. apolipoprotein E-lipid complexes bound to LDLR
2. phagocytosis of pathogens
3. C-type lectins bind mannose residues on glycolipids
4. scavenger receptors - bind modified LDL and apoptotic cells

Question 39

lipid loading and exchange

Answer 39

any one of the four mechanisms
then… exchange of lipids through actions of accessory molecules:

CD1e

Saposins - binds lipids, extracts from membranes and transfers to CD1 identified in several lipid storage disorders

Question 40

T or F. Pathogens interfere with antigen presentation pathways

Answer 40

T