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IHL Exam 2 > HLA & antigen processing(Bowden) > Flashcards

HLA & antigen processing(Bowden) Flashcards

1
Q

Where was histocompatability first identified

A

in mice

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2
Q

Can T cells recognize antigens in free soluble form

A

NO

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3
Q

Describe characteristic of HLA genes

A

tightly linked- highly polymorphic
more than 150 separate alleles
many alternative versions of each gene

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4
Q

What does the Class III locus of HLA encode for

A

complement proteins and cytokines

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5
Q

Where is are the HLA genes found and what are the 3 distinct classes

A 
short arm of chromosome 6
Class II(D region) then class III then class I
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6
Q

Describe HLA haplotype

A

total set of HLA alleles are present on each chromosome. Most have 1 from mom and 1 from dad–> CO DOMINANT expression

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7
Q

What loci are the Class I HLA genes found on

A

HLA-A B and C

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8
Q

Where are class I HLA molecules found

A

on all nucleated cells

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9
Q

What cells do class I HLA present to

A

CD8+ cytotoxic T cells

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10
Q

What is the structure of class I HLA

A

membrane bound glycoproteins formed by 4 extracellular globular domains
3 domains are alpha chains and one is B2 microglobulin

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11
Q

What proteins oh HLA class 1 are HLA encoded

A

just the alpha 1 2 and 3 domains

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12
Q

Where is the peptide cleft of HLA class 1

A

between alpha 1 and 2 domains-greatest polymorphism

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13
Q

How big is the peptide that can fit into cleft of HLA I, and what specific structure must it have

A

8-10 amino acids in length with CLOSED ends!

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14
Q

How can different peptides bind to HLA I clefts

A

each allele of Class I HLA has a different range that can bind in groove

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15
Q

How is the class I HLA formed

A

alpha chain translated in ER as glycoprotein and joins with B2 micro globulin
associates with peptides derived from cytosolic proteins and transported to cell surface

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16
Q

Describe class I HLA gene

A

regulatory sequences, leader sequence, 3 alpha domains, transmembrane cytoplasmic proteins

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17
Q

how many alleles of class I can be expressed

A

all!, 6 different HLAs slgihtly different shape and present different peptides

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18
Q

Where are HLA class II genes encoded

A

D region- 3 sets DP, DQ and DR

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19
Q

Where are class II HLA found

A

APC, dendritic cells and B cells

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20
Q

What cells do class II HLA present to?

A

CD4+ T cells

21
Q

Structure of Class II HLA

A

alpha and B chain- encoded by D region.

4 globular structure- alpha and beta not covalently linked

22
Q

Where is the peptide cleft in Class II HLA

A

between alpha and beta globular domains

23
Q

What is the general structure of peptides binding class II HLA

A

13-18 aa long, OPEN ENDS, conformation of groove dictates what can bind

24
Q

Synthesis of class II HLA

A

alpha and beta synthesized into ER, interact with third protein- the invariant chain
Enters endocytic compartment then transported to cell surface

25
Q

What is the role of the invariant chain in class II HLA

A

binds to alpha and beta, blockin peptide cleft to direct transport to endocytic compartment where it is degraded

26
Q

Why are Class II molecules put inside encytotic compartments

A

this is where they come in contact with antigens from outside of cell. So it can bind and then present them to T helper

27
Q

How many alleles are expressed in class II HLA

A

all alleles of both chains: 6 alpha, 6 beta. 3 from mom 3 from dad for each

28
Q

what is the purpose of any alpha chain binding to any beta chain

A

greater range of peptides that can bind to class II HLA

29
Q

What part of the peptide in the cleft is recognized by T cell

A

somewhere in between ends that bows outwards and sticks up

30
Q

HLA restriction rule

A

CD4+ only recognize Ag on Class II HLA

CD8+ only recognize Ag on Class I HLA

31
Q

What region in class I HLA binds to T cell R

A

alpha 3 regions bind CD8

32
Q

What region in class II HLA binds to t cell R

A

Beta 2 regions bind CD4

33
Q

3 maint types of APC

A

MAcrophages, Dendritic Cells, B cells

sometimes thymic epithelial cells

34
Q

Professional APC

A

Dendritic cells pincytose Ag and process it for presentation
most effective
produce co stimulatory molecules
activates naive CD4+ and CD8+ T cells

35
Q

How do Macrophages act as APC

A

phagocytose or pinocytose Ags- very good in activating memory T cells

36
Q

How do B cells act as APCs

A

bind soluble Ag via sIgs– high affinity
Ingest by pinocytosis
very effective at presenting to memory T cells

37
Q

Spleen vs lymph node caputure of Ag

A

spleen filters blood, lymph filets other fluid

38
Q

What happens when microbes are phagocytosed of pinocytosed

A

lose adhesive markers and upregulate CCR7 to increase expression of HLA and B7

39
Q

Intracellular pathogens activate what pathway

Extracell pathogens?

A 
Intra= Class I HLA
Extra= Class II HLA
40
Q

What dictates which pathway microbe enters

A

self vs non self, specific HLA binding site

density of protein and the chemical nature of fragment

41
Q

What stage is the endosome when HLA II loaded

A

late endosomes

42
Q

How is the invariant chain degraded

A

degraded to CLIP by lysosomal enzymes- HLA DM removes CLIP

43
Q

What happens if an HLA II is unbound

A

not presented on surface

44
Q

What is TAP in I HLA pathway

A

transports peptides from cytosol to interior of ER so it can be trimmed and loaded into class I HLA

45
Q

What is cross presentation

A

dendritic cells can present to both CD8 and CD4

46
Q

What type of diseases are associated with mutations of HLA alleles

A

autoimmune diseases

47
Q

Ankylosing spondylitis

A

inflammation of spine

problem in presentation encoded by HLA-B27 allele

48
Q

What are other examples of HLA associated diseases

A

rheumatic fever
Sjogrens syndrome
insulin dependent diabetes mellitus

49
Q

What happens wht TAP is down regulated in class I

A

renal cell carcinoma

IHL Exam 2 (11 decks)

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