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

1
Q

immune responsiveness

A

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

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2
Q

2 reasons for variability in immune responsiveness

A
  1. Determinant-selection model
  2. Holes-in-the-repertoire model
    * both appear to be correct
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3
Q

determinant selection model

A

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

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4
Q

holes-in-the-repertoire model

A

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

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5
Q

Ag processing and presentation pathways

A
  1. Cytosolic or endogenous processing: Class I

2. Exogenous processing: Class II

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6
Q

endogenous pathway general

A
  1. Proteasomes process peptides
  2. Peptides transported from cytosol to RER
  3. TAP
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7
Q

proteasomes

A
  • protease complexes where peptides are generated
  • tagged proteins are feed into them
    1. Constitutive: common
    2. Immuno
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8
Q

ubiquitin proteins

A

-used to ‘tag’ intracellular proteins for constitutive degradation

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9
Q

immunoproteasome

A
  • subtle variant

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

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10
Q

TAP

A
  • transporter associated with Ag processing
  • in RER membrane
  • move the peptide fragments
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11
Q

MHC I from ribosomes on RER

A

-anchor in RER membrane after translation

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12
Q

chaperones

A
  • aid peptide/MHC class I assembly
  • Calnexin, ERp57, calreticulin and tapasin
  • ER aminopeptidase (ERAP1)
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13
Q

calnexin, ERp57, calreticulin and tapasin

A

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

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14
Q

ERAP1

A

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

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15
Q

endogenous pathway steps

A
  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
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16
Q

PLC

A
  • calreticulin-tapasin-associated MHC class I molecule

* peptide loading complex

17
Q

exogenous pathway peptides

A

-generated from internalized Ags in endocytic vesicles

>particles are taken in with endosomes

18
Q

endosomes

A

-fuse with lysosome as an MHC late lysosome

19
Q

late lysosome

A

-becomse acidic and its contents are degraded

20
Q

simultaneously with endocytic vesicles

A

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

21
Q

invariant chain (Ii, CD74)

A
  • guides transport of class 2 MHC molecules to endocytic vesicles
  • prevents peptides from binding to groove too soon inER
  • uses sorting signals
22
Q

Ii sorting signals

A
  • in its cytoplasmic tail

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

23
Q

peptides assemble with MHC II molecules

A
  • Ii is degraded : CLIP

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

24
Q

Ii degraded

A
  • by proteolytic activity within endocytic compartments

* becomes Class II-assoiciated invariant chain (CLIP)

25
Q

HLA-DO

A

-prevents CLIP from being switched out

26
Q

exogeneous pathway steps

A
  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
27
Q

cross prevent exogenous Ag via MHC I molecules

A
  • exogenous Ag internalized by DC can access the endogenous pathway
  • mechanisms and functions are unclear
28
Q

to prevent re-direction of self Ags into APC pathways

A
  • 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

29
Q

‘license’

A

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

30
Q

DC

A

-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

31
Q

nonprotein Ag

A
  • some can be recognized by T-cells

- presentation not via classic MHC molecules

32
Q

CD1 and MHC I-related protein, MR1

A
  • family of nonclassical class I molecules

- can present lipids, lipid-linked molecules and MR1 metabolites of vitamin B2

33
Q

CD1 and MR1 simple

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