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Immunology > Lecture 4: MHC & Ag Presentation to TCells > Flashcards

Lecture 4: MHC & Ag Presentation to TCells Flashcards

1
Q

Bare Lymphocyte Syndrome is a form of _____ caused by…

A

SCID

Mutations in MHC (either type 1 or type 2)

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2
Q

T cell recognizes antigen via ______ molecule on an APC

A

MHC

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3
Q

Major class 1 genes are…

A

HLA - A,B,C

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4
Q

Minor class 1 genes

A

HLA – E,F,G,H,J,X

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5
Q

Major Class II genes

A

*HLA-D*

DP – A1,A2, B1,B2

DQ – A1, A2, B1, B2, B3

DR – A, B1, B2, B3

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6
Q

Major Class III genes are _________ and have _______________

A

Diverse

Non-antigen presenting functions

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7
Q

Class ___ region of HLA are the farthest

A

Class I

BCE AGF

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8
Q

Class ____ region is the closest on the HLA complex

A

Class II

DP, DQ, DR

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9
Q

HLA genes that are not expressed (not funcitonal) are referred to as _______

A

pseudogenes

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10
Q

The MHC on every human chromosome 6 contains one gene for ____ and _____

A

DRA

DRB1

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11
Q

Any ____ chain can pair with the ____ chain to form a class II Molecule

A

DR-B

DR-a

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12
Q

MHC I structural domains

A

alpha 1 + 2 + 3

beta 2

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13
Q

MHC I – peptide binding site formed by _____ domains

A

a1 + a2

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14
Q

MHC I Molecule is anchored to cell membrane by ____ domain(s)

A

a3

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15
Q

B2 microglobulin is ________ but __________

A

invariant but essential

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16
Q

The alpha chain of MHC is also known as the _____ chain

A

heavy

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17
Q

MHC II is composed of one ___ chain and one ____ chain

A

one alpha and one beta chain

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18
Q

MHC II peptide binding site is composed of ______ domain(s)

A

a1 and b1

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19
Q

For MHC II, which chains are variable and which are constant?

A

a1 + b1 are polymorphic (variable)

a2 + b2 domains are constant

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20
Q

T cell structural domains:

A

V-alpha + V-beta

C-alpha + C-beta

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21
Q

T cell antigen binding region comprised of ___ and ____ domains

A

V a/b

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22
Q

The peptide binding groove of MHC molecules is made of about ____ peptides

A

8 - 15

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23
Q

Rank the top three MHC I HLA’s in terms of polymorphism.

What cells do these correspond to?

A

B > A > C

CD8 T-cells + NK cells

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24
Q

MHC class I effect on CD8+ cells and NK cells?

A

Activate CD8+ cells

Inhibit NK cells

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25
Q

Polymorphism definition…

A

presence of multiple alternative alleles of a gene

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26
Q

What is, by far, the most highly polymorphic MHC II allele?

A

DRB1

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27
Q

DMA/DMB

DOA/DOB

These genes serve what function in MHCII

A

Help peptide loading

O+M

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28
Q

DP, DQ, and DR genes provide what function for MHC II

A

Present antigen peptides to CD4+ Tcells

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29
Q

Polymorphism allows the human population to ___________

A

hadle a variety of pathogens

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30
Q

MHC genes exhibit _______.

_______ are expressed.

A

Co-Dominance

Both alleles are expressed

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31
Q

In any mating, ______ possible combinations of haplotypes can be found in the offspring (for MHC molecules)

A

4 combinations

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32
Q

(With regard to chromosome 6) A **haplotype **is a…

A

particular combination of MHC alleles found on a given chromosome 6

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33
Q

HLA -E and HLA-G are ____ and interact with ______

A

Oligomorphic

NK cell receptors

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34
Q

HLA-F function

A

Unknown. It remains intracellular with a SINGLE isotype.

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35
Q

Common function to HLA A, B, and C?

A

Present Antigen to CD8+ cells

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36
Q

Common function to HLA-DP, DQ, and DR?

A

Present antigen to CD4+ cells

37
Q

____ is the most highly polymorphic allele for MHC-II

A

HLA-DRB1

38
Q

MHC class II variablity is due to the ___ domain because the _____ chain is monomorphic

A

Beta 1 domain

The alpha domain is **monomorphic **(a1+a2)

39
Q

Each MHC molecule binds a characteristic set of peptides. ________ in these peptides are important for binding to MHC

A

Anchor residues

40
Q

What is “degenerate binding”

A

the property which allows each MHC molecule to handle many different peptides

41
Q

MHC I molecules bind mostly _____ peptides, and positions __ and __ are the usual anchor residues.

A

Nonamer peptides

Positions 2 and 9

42
Q

Some MHC II can have mor ethan 3 isotpes because there may be more than one _____. This means a cell will have what combination?

A

DR gene

DRB1 + DRA (like all cells) WITH either DRB3, DRB4, or *DRB5 *

43
Q

(In both MHC I and II) which are the most polymorphic

A

HLA-B and HLA-DRB1

44
Q

____ is most monomorphic HLA

A

HLA-DR-α

45
Q

HLA _______ are present in only some people

A

HLA DRB3, DRB4, DRB5

46
Q

Most people are ______ (genetically) and express ________

A

Heterozygotes

Two Haplotypes

47
Q

A person can express _____ Class I isoforms and ______ Class II isoforms.

A

3-6

3-8

48
Q

There are _____ MHC I isoforms and _____ MHC II isoforms in the human population

A

753 Class I

2406 Class II

49
Q

MHC__ is expressed in all cells

A

MHC 1

50
Q

These four cells are the only ones to express high levels of both MHC 1 and II molecules.

A

B cells

MQ

DC

Thymic epithelial cells

51
Q

These are the three APC cells

A

B cells, MQ, DC

52
Q

_______ do not express either MHC I or II

A

Erythrocytes

53
Q

___ increased MHC II expression in APC’s. What is the other effect?

A

IFN - Gamma

it induces the expression of MHC II in non-APC’s at the sites of infection

54
Q

MHC II handles ____ antigens

A

Extracellular

55
Q

Antigen processing for MHC II (process)

A
  • Extracellular ag endocytosed
  • -> phagolysosome
  • MHC II in vesicle goes and binds Ag
  • MHC II presents the Ag at the surface
56
Q

MHC Class I handles ____ antigens

A

Intracellular

57
Q

MHC class I Antigen processing (steps)

A

Ag in cytoplasm is ubiquinated

-> Proteosome

Transport to ER

Bind MHC *in ER*

Presented at surface

58
Q

Intracellular Ag’s are handled by _____ and they can originate from ___ (such as ___)

A

MHC I

viruses (such as HIV)

59
Q

MHC I proteins are assembled in ER and associate with ___ and ___

A

TAP protein

Calnexin (Chaperone)

60
Q

TCR’s do not bind to ___ but rather to ____

A

Dont bind whole antigens

instead bind to antigen peptides

61
Q

Transport of peptides to ER requires

A

TAP

Transporter associated with Antigen Processing

62
Q

What happens when you don’t have TAP protein

A

Bare Lymphocyte syndrome

_No TAP _ = No MHC1 = _No CD8+ _ = No Cytotoxicity

= Chronic Respiratory infection

63
Q

TAP is made of

A

TAP1 + TAP2

64
Q

_____ length polypeptides are transported via TAP

A

8 or more amino acids

65
Q

MHC1 cant ______ without peptides being loaded

A

can’t leave ER

66
Q

Three molecular chaperones that aid in MHC folding and loading of peptides:

A

Calnexin

Calreticulin

Tapasin

67
Q

MHC class 1 is stabilized by ____ in ER until ____ binds

A

Calnexin

B2

68
Q

In absence of infection, _____ are presented on MHC but these ________

A

self peptides

do not activate T cells

69
Q

After synthesis in the ER, MHC 2 peptide binding site is protected by

A

CLIP region of **Ii **

(Invariant chaperone)

70
Q

CLIP is removed from MHC II by _____

A

HLA DM protein

71
Q

____, ___, and ____ guide the peptide loading of MHC II

A

invariant chain

CLIP

HLA-DM

72
Q

What must happen after CLIP is gone?

A

MHC II needs to bind to peptide or it will be degraded

73
Q

Where do MHC II bind to peptides?

A

In fused vesicles

74
Q

CD8 ___ group binds to the ____ group on the MHC molecule

A

CD8 alpha group binds to a3 on MHC1

75
Q

CD4 binds to ____ group on MHCII

A

B2 group

76
Q

T cell receptor recognitionof antigens is _________

A

MHC restricted

A TCR may not recognize a particular peptide when it is bound to a different class of MHC, or a different peptide on the *same *MHC

77
Q

CD8 kills virus infected cells how?

A

directly

78
Q

CD4 T cell does what to stimulate other cells?

A

Makes cytokines

Activate macrophage to make its own cytokines

Activate B cells (to plasma cell) to make Antibodies

79
Q

HLA typing is dome via what methods

A

Microcytotoxicity Assay

RFLP

PCR

Flow Cytometry/ELISA

80
Q

Microtoxicity Assay uses ____ which is mixed with lymphocytes

Exogenous complement is added which results in ….

A

Anti-HLA serum

results in lysis of cells that have bound Antibody

81
Q

During RFLP, DNa is digested and hybridized to

A

Radiolabeled MHC

82
Q

PCR uses

A

MHC specific primers

83
Q

ELISA uses

A

monoclonal antibodies to MHC alleles

84
Q

Other test for HLA compatibility

What are we looking for?

A

Mixed Lymphocyte Reaction test

Higher response = higher the match

85
Q

Disease for DR3 + DR2

A

SLE

86
Q

Disease for DR4

A

Rheumatoid Arthritis

87
Q

DIsease for B7 and DR2

A

MS

88
Q

Disease for B8 + DR3 + DR4

A

T1DM

89
Q

Disease for B27

A

Ankylosing Spondylitis

Immunology (10 decks)

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