Lecture 15: Immune System Protein Trafficking + viruses Flashcards

1
Q

MHC stands for ___

A

Major Histocompatibility Complex

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2
Q

MHC are ____ on ___

A

Oligomeric protein complexes on the cell surface

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3
Q

MHC is ___ meaning that it has multiple alleles

A

polymorphic

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4
Q

MHC binds to ____ (___ amino acids)

A

wide variety of peptide antigens (8-24 a.a)

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5
Q

MHC (general) presents antigens to ____

A

T-cells

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6
Q

antigens to MHC I cause ___ while antigens to MHC II cause ___

A

cell death
T-cell stimulation

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7
Q

MHC complexes rich the cell surface with ___ using ____

A

bound peptide antigens
different trafficking pathways

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8
Q

class MHC I description

A

a-chain (transmembrane heavy chain)-polymorphic
->a1 +a2 =peptide binding groove
b-microglobulin - non polymorphic/ soluble

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9
Q

class MHC II description

A

a-chain + b-chain (transmembrane region)- 2 chains
a1 +b1 =peptide binding groove (polymorphic)

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10
Q

MHC I is present only in ___

A

nucleated cells (not in blood cells) in vertebrates

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11
Q

MHC II is present only in ____

A

antigens presenting cells (ex. dendritic cells, b-cells, macrophages)

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12
Q

MHC I presents antigen to ___

A

cytotoxic T-cells

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13
Q

MHC II presents antigen to ___

A

helper + regulatory T-cells

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14
Q

source of peptide antigen (MHC I)

A

-proteins made in cytoplasm

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15
Q

source of peptide antigen (MHC II)

A

endocytosis PM + extracellular proteins

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16
Q

If antigen on MHC I is foreign then ____

A

the cell is targeted for destruction

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17
Q

receptor on cytotoxic T-cell that recognizes MHC I

A

CD8

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18
Q

general structure of MHC I

A

heterodimer

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19
Q

a-chain of MHC is ____ membrane protein

A

Type-1

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20
Q

complete assembly of MHC I occurs in ___

A

ER

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21
Q

a-chain of MHC I associate with __, __, ___ before/during assembly in ____

A

calnexin*, calreticulin and ERp57
ER lumen

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22
Q

a-chain of MHC I associate with B-microglobulin
when?

A

-shortly after synthesis (2 min)

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23
Q

peptide binding groove of MHC I protein faces ___

A

lumen of ER

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24
Q

antigens (peptides) for MHC I are transported from ____ into ____ by ____

A

*cytosol into ER lumen by TAP

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25
Q

TAP is a ____ in ER membrane, ____-ase, & ____

A

Transporter
ATP-ase
heterodimer (TAP-1,TAP-2)

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26
Q

transport of antigens for MHC I into ER lumen is a ___-dependent process

A

ATP

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27
Q

peptides for MHC I (viral) are derived from ____

A

proteolysis of newly synthesized viral proteins in
cytosol by Proteasome

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28
Q

Tapasin (Tsn) is an _____associated with

A

ER membrane glycoprotein
TAP

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29
Q

Function of Tapasin

A

Facilitates peptide loading onto MHC I

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30
Q

___ motif on Tsn retains unloaded MHC I in ER

A

KK

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31
Q

Tsn has a ____(ER-retention) motif

A

dilysine

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32
Q

TAP has a ____(NBD) for __ binding

A

nucleotide binding domain
ATP

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33
Q

Tsn and fully loaded MHC I

A

Tsn releases MHC I to move to golgi and then cell surface

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34
Q

MHC I acts as a ___ for T-cell

A

a window

35
Q

cytotoxic cell needs very little ___

A

cytoplasm (mostly nucleus)

36
Q

In un-infected cells, most MHC I complexes are occupied by _____

A

peptides derived from cellular proteins (mostly defective proteins from ribosomes, some retirees)

37
Q

In infected cells, most MHC I complexes are occupied by _____

A

viral peptides

38
Q

state of MHC when cell is not fighting infection

A

-bound but with host proteins

39
Q

receptor on helper T-cell that recognizes MHC II

A

CD4

40
Q

MHC II a and B chain are both ___

A

type 1 membrane glycoproteins

41
Q

peptide binding groove of MHC I binds peptides with ___ a.a

A

8-10

42
Q

peptide binding groove of MHC II binds peptides with ___ a.a

A

12-20

43
Q

assembly of MHC II begins in ____ and requires ___

A

ER
chaperones

44
Q

invariant chain facilitates transport of _____

A

MHC II complexes to endosomes

45
Q

invariant chain prevents ___

A

binding of peptides to MHC II in ER (don’t want MHC I peptides)

46
Q

invariant chain is a ____

A

nonpolymorphic transmembrane protein(homotrimer)

47
Q

invariant chain stimulates ___

A

exit of MHC II heterodimers from ER

48
Q

invariant chain _____ peptide binding groove of MHC II by _____ in _____

A

is removed
proteolysis
endosomes

49
Q

peptides of MHC II are derived from ___

A

degraded endocytosed material (bacteria, viruses) from cell surface

50
Q

Proteasome _____ required to generate peptides for binding to MHC II

A

is not

51
Q

After removal of invariant chain, MHC II binds to peptide in _____ which ____ complex

A

endosomes
stabilizes

52
Q

invariant chain contains ___ motif in ____

A

dileucine (LL/ML)
cytoplasmic domain

53
Q

Viral immune evasion strategies

A

-Avoiding antibodies-changing of surface proteins (flu,cold,coronaviruses)
-Viral proteins that modulate host immune response

54
Q

How do viral proteins modulate host immune response?

A

-Blocking expression of cytokines and prevention of
programmed cell death (apoptosis)
– Interfering with cellular immune response by disabling peptide
presentation or impairing NK cell function

55
Q

Viral Interference with MHC I Function (Post-Translational): generation of peptides

A

EBNA-1 protein contains Gly-Ala repeats which interferes with proteasome (no peptides degrades so no assembly on MHC I and export from ER)

56
Q

Viral Interference with MHC I Function (Post-Translational): peptide transport in ER

A

-competes for peptide-binding of TAP
-stabilizes TAP in conformation that it can’t bind to ATP
result: no peptides in ER, no assembly of MHC I, no export from ER

57
Q

E3-19K is a ____

A

“immunosubversive” protein encoded by adenoviruses

58
Q

adenoviruses are ___

A

small DNA viruses (often cause cold-like symptoms)

59
Q

E3-19K has which motif?

A

KK motif in cytoplasm

60
Q

E3-19K blocks the expression of ___ at _____ by preventing the ______

A

MHC I
cell surface
conversion of N-linked sugar into Endo H resistant forms

61
Q

E3-19K binds to and retains MHC I in ___

A

ER

62
Q

E3-19K also binds to ___ and prevents binding to ____

A

TAP
tapasin (peptide-loading)

63
Q

CMV US3 and US10 have same function as ___ but don’t prevent ___

A

E3-19K
peptide loading

64
Q

CMV US2 and US11 bind to ___ in___ and cause

A

MHC I
ER
dislocation

65
Q

US11 localizes where?

A

in ER

66
Q

proteasome inhibitor

A

ZL3VS

67
Q

____inhibits US11-induced degradation of MHC (HC-heavy chain)

A

Blocking proteasome

68
Q

US-11 leads to expression of ____

A

soluble, deglycosylated MHC I HC

69
Q

Differential centrifugation refresher

A

-Start from cell homogenate
-Spin at different speeds (g force) for various times
-Obtain several fractions that are enriched in cell components (e.g. membranes) of various sizes

70
Q

Differential centrifugation 1000 x g pellet

A

-whole cells, nuclei, cytoskeletons

71
Q

Differential centrifugation 10,000 x g pellet

A

-mitochondria, lysosomes, peroxisomes

72
Q

Differential centrifugation 100,000 x g pellet

A

microsomes, small vesicles

73
Q

HIV Nef protein has multiple functions

A
  • Not required for replication
  • Involved in immune deficiency
74
Q

Nef protein operates ____

A

post ER/Golgi

75
Q

Nef-induced degradation of ____ is blocked by inhibitors of ____

A

mature MHC-I
acidic degradation

76
Q

Lactacystine (Lact) inhibits____

A

proteasome

77
Q

Bafilomycin (Baf A1) inhibits ___

A

proton pump in lysosomes

78
Q

NH4Cl raises _____

A

pH of lysosomes

79
Q

both bafilomycin +NH4Cl ___

A

disrupts function of lysosomes

80
Q

HIV Nef causes _____

A

lysosomal-dependent degradation of MHC I (needs AP-1)

81
Q

depletion of AP-1 effect on Nef-dependent degradation of MHC I

A

-inhibits degradation of MHC I(AP-1 moves MHC I from golgi to lysosomes)

82
Q

______ interacts with AP-2 to accelerate endocytosis of CD4 and MHC-1, leading to ____

A

HIV-Nef
selective removal of MHC I from surface of presenting cell

83
Q

interference of MHC II mostly occurs in ___

A

endocytic pathway

84
Q

Papilloma viruses + MHC II interference

A

produces E5 protein: replace subunit of proton pump
-pH in endosomes/lysosomes increases
-Proteolysis of endocytosed material is blocked
-no peptide-loading of MHC II
-decreased cell surface
expression of MHC II