BIOL 435 Ch. 7 p.2 (MHC and Ag Presentation)

Question 1

immune responsiveness

Answer 1

-different capability of MHC II alleles to present Ag may dictate overall strength of immune response between individuals

Question 2

2 reasons for variability in immune responsiveness

Answer 2

1. Determinant-selection model
2. Holes-in-the-repertoire model
   * both appear to be correct

Question 3

determinant selection model

Answer 3

-MHC class 2 molecules differ in ability to bind particular processed Ag peptides

Question 4

holes-in-the-repertoire model

Answer 4

-T cells with TCRs that recognize foreign Ags closely resembling self-Ags may be eliminated during thymic development

Question 5

Ag processing and presentation pathways

Answer 5

1. Cytosolic or endogenous processing: Class I

2. Exogenous processing: Class II

Question 6

endogenous pathway general

Answer 6

1. Proteasomes process peptides
2. Peptides transported from cytosol to RER
3. TAP

Question 7

proteasomes

Answer 7

• protease complexes where peptides are generated
• tagged proteins are feed into them
  1. Constitutive: common
  2. Immuno

Question 8

ubiquitin proteins

Answer 8

-used to ‘tag’ intracellular proteins for constitutive degradation

Question 9

immunoproteasome

Answer 9

• subtle variant

- cleaves ubiquitinate proteins into fragments that pair better with MHC molecules

Question 10

TAP

Answer 10

• transporter associated with Ag processing
• in RER membrane
• move the peptide fragments

Question 11

MHC I from ribosomes on RER

Answer 11

-anchor in RER membrane after translation

Question 12

chaperones

Answer 12

• aid peptide/MHC class I assembly
• Calnexin, ERp57, calreticulin and tapasin
• ER aminopeptidase (ERAP1)

Question 13

calnexin, ERp57, calreticulin and tapasin

Answer 13

-help fold MHC I and put it in close proximity to TAP

Question 14

ERAP1

Answer 14

-trims long peptides to a suitable size for MHC I grooves

Question 15

endogenous pathway steps

Answer 15

1. MHC I, Calnexin and ERp57
2. Calnexin leaves, and beta2 microglobulin, tapasin and calreticulin join (PLC)
3. Close to TAP
4. ERAP trims peptide
5. Peptides into groove
   >ERp57, calreticulin and tapasin leave

Question 16

PLC

Answer 16

• calreticulin-tapasin-associated MHC class I molecule

* peptide loading complex

Question 17

exogenous pathway peptides

Answer 17

-generated from internalized Ags in endocytic vesicles

>particles are taken in with endosomes

Question 18

endosomes

Answer 18

-fuse with lysosome as an MHC late lysosome

Question 19

late lysosome

Answer 19

-becomse acidic and its contents are degraded

Question 20

simultaneously with endocytic vesicles

Answer 20

-MHC II molecules are produced
>associated with invariant chain (Ii, CD74)
>exported in vesicles from ER to Golgi

Question 21

invariant chain (Ii, CD74)

Answer 21

• guides transport of class 2 MHC molecules to endocytic vesicles
• prevents peptides from binding to groove too soon inER
• uses sorting signals

Question 22

Ii sorting signals

Answer 22

• in its cytoplasmic tail

- direct MHC II molecules (contain vesicles to peptide) containing endocytic compartments

Question 23

peptides assemble with MHC II molecules

Answer 23

• Ii is degraded : CLIP

- HLA-DM exchanges CLIP out of groove for a peptide fragment

Question 24

Ii degraded

Answer 24

• by proteolytic activity within endocytic compartments

* becomes Class II-assoiciated invariant chain (CLIP)

Question 25

HLA-DO

Answer 25

-prevents CLIP from being switched out

Question 26

exogeneous pathway steps

Answer 26

1. Invariant chain binds MHC II alpha and beta chains 2. Goes through Golgi 3. Invariant chain degraded: CLIP 4. Exogenous Ag take up 5. HLA-DM exchanges CLIP for Ag peptide 6. MHC-peptide transported to PM

Question 27

cross prevent exogenous Ag via MHC I molecules

Answer 27

- exogenous Ag internalized by DC can access the endogenous pathway - mechanisms and functions are unclear

Question 28

to prevent re-direction of self Ags into APC pathways

Answer 28

- DC may need 'license' | - if DC can present foreign Ag to CD4+ T helper cell, it gets license to redirect exogenous Ag into endogenous pathway

Question 29

'license'

Answer 29

-might be back/forth cytokine signal between APC and helper T-cell >a situation right for cross presentation

Question 30

DC

Answer 30

-primary cross-presenting cell type -exogenous Ag redirected to endogenous pathway >allows their presentation on MHC I, priming CD8+ T-cell response *only APC to exhibit this activity in vivo

Question 31

nonprotein Ag

Answer 31

- some can be recognized by T-cells | - presentation not via classic MHC molecules

Question 32

CD1 and MHC I-related protein, MR1

Answer 32

- family of nonclassical class I molecules | - can present lipids, lipid-linked molecules and MR1 metabolites of vitamin B2

Question 33

CD1 and MR1 simple

Answer 33

- 5 CD1 - 1 MR1 - very little polymorphism is displayed - most function similarly to MHC class 2 molecules * deep binding pocket=characteristic of CD1