HLA & antigen processing(Bowden)

Question 1

Where was histocompatability first identified

Answer 1

in mice

Question 2

Can T cells recognize antigens in free soluble form

Answer 2

NO

Question 3

Describe characteristic of HLA genes

Answer 3

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

Question 4

What does the Class III locus of HLA encode for

Answer 4

complement proteins and cytokines

Question 5

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

Answer 5

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

Question 6

Describe HLA haplotype

Answer 6

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

Question 7

What loci are the Class I HLA genes found on

Answer 7

HLA-A B and C

Question 8

Where are class I HLA molecules found

Answer 8

on all nucleated cells

Question 9

What cells do class I HLA present to

Answer 9

CD8+ cytotoxic T cells

Question 10

What is the structure of class I HLA

Answer 10

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

Question 11

What proteins oh HLA class 1 are HLA encoded

Answer 11

just the alpha 1 2 and 3 domains

Question 12

Where is the peptide cleft of HLA class 1

Answer 12

between alpha 1 and 2 domains-greatest polymorphism

Question 13

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

Answer 13

8-10 amino acids in length with CLOSED ends!

Question 14

How can different peptides bind to HLA I clefts

Answer 14

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

Question 15

How is the class I HLA formed

Answer 15

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

Question 16

Describe class I HLA gene

Answer 16

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

Question 17

how many alleles of class I can be expressed

Answer 17

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

Question 18

Where are HLA class II genes encoded

Answer 18

D region- 3 sets DP, DQ and DR

Question 19

Where are class II HLA found

Answer 19

APC, dendritic cells and B cells

Question 20

What cells do class II HLA present to?

Answer 20

CD4+ T cells

Question 21

Structure of Class II HLA

Answer 21

alpha and B chain- encoded by D region.

4 globular structure- alpha and beta not covalently linked

Question 22

Where is the peptide cleft in Class II HLA

Answer 22

between alpha and beta globular domains

Question 23

What is the general structure of peptides binding class II HLA

Answer 23

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

Question 24

Synthesis of class II HLA

Answer 24

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

Question 25

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

Answer 25

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

Question 26

Why are Class II molecules put inside encytotic compartments

Answer 26

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

Question 27

How many alleles are expressed in class II HLA

Answer 27

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

Question 28

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

Answer 28

greater range of peptides that can bind to class II HLA

Question 29

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

Answer 29

somewhere in between ends that bows outwards and sticks up

Question 30

HLA restriction rule

Answer 30

CD4+ only recognize Ag on Class II HLA | CD8+ only recognize Ag on Class I HLA

Question 31

What region in class I HLA binds to T cell R

Answer 31

alpha 3 regions bind CD8

Question 32

What region in class II HLA binds to t cell R

Answer 32

Beta 2 regions bind CD4

Question 33

3 maint types of APC

Answer 33

MAcrophages, Dendritic Cells, B cells | sometimes thymic epithelial cells

Question 34

Professional APC

Answer 34

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

Question 35

How do Macrophages act as APC

Answer 35

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

Question 36

How do B cells act as APCs

Answer 36

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

Question 37

Spleen vs lymph node caputure of Ag

Answer 37

spleen filters blood, lymph filets other fluid

Question 38

What happens when microbes are phagocytosed of pinocytosed

Answer 38

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

Question 39

Intracellular pathogens activate what pathway | Extracell pathogens?

Answer 39

``` Intra= Class I HLA Extra= Class II HLA ```

Question 40

What dictates which pathway microbe enters

Answer 40

self vs non self, specific HLA binding site | density of protein and the chemical nature of fragment

Question 41

What stage is the endosome when HLA II loaded

Answer 41

late endosomes

Question 42

How is the invariant chain degraded

Answer 42

degraded to CLIP by lysosomal enzymes- HLA DM removes CLIP

Question 43

What happens if an HLA II is unbound

Answer 43

not presented on surface

Question 44

What is TAP in I HLA pathway

Answer 44

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

Question 45

What is cross presentation

Answer 45

dendritic cells can present to both CD8 and CD4

Question 46

What type of diseases are associated with mutations of HLA alleles

Answer 46

autoimmune diseases

Question 47

Ankylosing spondylitis

Answer 47

inflammation of spine | problem in presentation encoded by HLA-B27 allele

Question 48

What are other examples of HLA associated diseases

Answer 48

rheumatic fever Sjogrens syndrome insulin dependent diabetes mellitus

Question 49

What happens wht TAP is down regulated in class I

Answer 49

renal cell carcinoma