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Spring 2022 > BIOL 435 Ch. 7 p.1 (MHC and Ag Presentation) > Flashcards

BIOL 435 Ch. 7 p.1 (MHC and Ag Presentation) Flashcards

1
Q

MHC class I structure

A

-member of Ig super family
>posses Ig domains
1. Small 12 kDa beta 2 microglobulin
2. Larger 45 kDa glycoprotein alpha chain

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2
Q

45kDa alpha chain

A

-3 external domains
>each ~90AA in length
-transmembrane domain of 25AA
-cytoplasmic anchor

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3
Q

alpha 1 and 2 (MHC I)

A

-form a cleft region

>binds an 8-10 AA long peptide fragment from an Ag

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4
Q

cleft (MHC I)

A
  • a beta-sheet forms the floor

- 2 alpha helices form the walls

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5
Q

MHC I interactions

A
  • present peptides to CD8 T cells
  • peptides derived from endogenous intracellular proteins
  • AA anchor peptide into groove
  • otherAA interact with TCR
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6
Q

MHC I peptide length

A
  • 8-10AA long

* 9AA

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7
Q

MHC II structure

A 
-member of Ig superfamily
>posses Ig domains
-heterodimeric
>33kDa alpha-chain
>28kDa beta-chain
-both chains pass through PM
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8
Q

peptide binding cleft (MHC II)

A
  • formed by pairing alpha1 and beta1 domains
  • 8 antiparalell beta-strand=floor
  • alpha helices=sides
  • accomadates 13-18AA long peptides
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9
Q

MHC II interactions

A
  • present peptides to CD4 T cells
  • peptides from exogenous proteins
  • some AA anchor peptide into groove
  • other AA interact with TCR
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10
Q

polymorphism

A

-class I and II exhibit it in the peptide binding region
-several hundreds different alleleic variants
>up to 6 MHC I
>up to 12 MHC II

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11
Q

a given MHC

A
  • can bind numerous different peptides
  • some peptides can bind several different MHC
  • a few key anchor AA
  • increased diversity
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12
Q

human leukocyte Ag (HLA) complex

A 
-class 1, 2 and 3 MHC genes
>class 1: 3 alpha
>class 2: 3 alpha and beta
>class 3: 2
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13
Q

class I MHC genes

A
  • expressed on surface of nearly all nucleated cells

- major function=present endogenous (cytosolic) peptide Ag to CD8 T-cells

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14
Q

class II MH genes

A
  • expressed on APCs (macrophages, dendritic cells and B-cells)
  • major function=present exogenous (extracellular) peptide Ag to CD4 T-cells
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15
Q

class III MHC genes

A

-encode diverse set of proteins
>some with immune functions
-no direct role in Ag presentation to T-cells
Ex. C’ and inflammatory proteins

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16
Q

haplotypes

A

-allelic forms of MHC genes inherited in linked groups
>lie close together
-one per parent

17
Q

inbreeding in mice

A

-has allowed for more standardized MHC genotypes to control variability
Ex. syngeneic and congenic

18
Q

syngeneic

A

-identical at all genetic loci

>3 vs. 6

19
Q

congeneic

A

-genetically identical expect at a single genetic region

20
Q

MHC alleles codominantly expressed

A
  • both maternal and paternal MHC genes are expressed in offspring cells
  • best chance to have SOME capability of presenting all possible Ag peptides it encounters
  • makes transplantation difficult (heterozygous at each locus)
21
Q

class I/II diversity at 2 levels

A
  • individual

- species

22
Q

individual/species diversity

A

-MHC alleles inherited from both parents
-alleles can differ among individuals =enormous diversity
>provides flexibility in responding to unexpected environmental changes

23
Q

MHC region is

A

-polygeneic

24
Q

heterozygous individuals

A

-express gene products encoded by alleles at each MHC gene locus

25
Q

each parental allele’s

A

-are codominantly expressed

26
Q

MHC polymorphism: functional relevance

A
  • differences tend to be clustered at AA locations within the groove stie
  • if changed elsewhere too much, the conformation may not bind anything
27
Q

intracellular Ag peptides (MHC I)

A

-includes self-proteins
-provides a way of ‘checking’ that cells are self and healthy
-can show which cells have been infected with viruses and are abnormal
>display peptides and activate cytotoxic T-cells

28
Q

extracellular Ag peptides (MHC II)

A

-more restricted
-found on cells involved in immune response
-helps direct responses against threats
>display peptides and activate T helper cells

29
Q

MHC I expression

A

-found throughout the body

>essentially on all nucleated cells

30
Q

MHC II expression

A
  • primarily restricted to Ag-presenting cells

- macrophages, dendritic cells and B cells

31
Q

none pAPC

A
  • mTEC
  • cTEC
  • fibroblasts of skin
  • glial cells in brain
  • beta-cells in pancreas
  • vascular epithelial cells
  • express MHC II only under certain conditions

Spring 2022 (54 decks)

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