Lecture 10 - MHCs

Question 1

What type of molecules are MHC receptors

Answer 1

glycoproteins

Question 2

an antigen fragment can trigger immune response only if it is

Answer 2

bound to an MHC molecule

Question 3

What consequence does MHC control of antigen presenting have

Answer 3

determines animal’s susceptibility to infectious or autoimmune diseases

Question 4

three classes of MHC gene loci

Answer 4

I, II, III

Question 5

Genes in class I codes for

Answer 5

MHC I molecules that are present on all nucleated cells

Question 6

Genes in class II codes for

Answer 6

MHC II molecules that are restricted to professional APCs

Question 7

Genes in class III codes for

Answer 7

a diverse mixture of proteins, many of which are
important in innate immunity, such as complement proteins

Question 8

MHC I distribution

Answer 8

most nucleated cells except mammalian red cells, gametes, neurons, trophoblast cells

Question 9

MHC II distribution

Answer 9

B cells, macrophages, DC

Question 10

MHC I function

Answer 10

present antigen to cytotoxic T cells

Question 11

MHC II function

Answer 11

present antigen to T helper cells

Question 12

MHC I result

Answer 12

T cell mediated toxicity

Question 13

MHC II result

Answer 13

T cell mediated help

Question 14

HLA

Answer 14

human leukocyte antigen

Question 15

DLA

Answer 15

dog leukocyte antigen

Question 16

BoLA

Answer 16

bovine leukocyte antigen

Question 17

ELA

Answer 17

equine leukocyte antigen

Question 18

H-2

Answer 18

mouse leukocyte antigen

Question 19

B

Answer 19

chicken leukocyte antigen

Question 20

MHC Class Ia

Answer 20

Expressed on most nucleated cells. Only polymorphic class I molecules

Question 21

MHC Class Ib

Answer 21

Reduced expression and tissue distribution compared
with class Ia molecules. These bind to a limited range of ligands. Receptors for PAMPs

Question 22

MHC Class Ic

Answer 22

MICA and MICB, involved in signaling to NK cells but do not bind antigenic peptides

Question 23

MHC Class Id

Answer 23

bind to PAMPs

Question 24

Structure of MHC class Ia molecule

Answer 24

2 long chains

Question 25

MHC class Ia 2 chains

Answer 25

1. long heavy a chain 2. short B2-microglobulin chain

Question 26

long heavy a chain

Answer 26

three extracellular domains; a transmembrane domain; a cytoplasmic domain

Question 27

short β2-microglobulin chain

Answer 27

attached to the extracellular region of the heavy α chain

Question 28

Where do small peptides bind on long heavy a chain

Answer 28

groove, antigen binding site formed by a1 and a2 domains

Question 29

Heavy a chain is ____ while B2-microglobulin chain is ____

Answer 29

polymorphic; monomorphic

Question 30

B2 microglobulin chain serves to

Answer 30

stabilize the structure

Question 31

Peptides that bind to MHC I are

Answer 31

8-10 amino acids long; anchored at both ends and fit completely within the binding groove

Question 32

The amino acids at each end of peptide must conform to

Answer 32

particular motif

Question 33

Why can AA in middle of peptide be variable

Answer 33

do not interact with AA within the groove

Question 34

MHC I molecules present _____ which are derived from proteins manufactured by or within the cell

Answer 34

endogenous peptides

Question 35

Endogenous peptides can be

Answer 35

normal proteins or viral proteins if the virus is replicating inside the cell

Question 36

Steps of the endogenous pathway of MHC I 1. ____ binds to the cytoplasmic protein and targets it to ____ 2. ____ is a cellular organelle that is a hollow cylinder and ___ proteins into short peptides 3. _____ bind cytosoloic peptides from the proteasome and transport them to the _____ of the ____ 4. Peptide is trimmed to 9 aa by the ____ and binds to an empty ____ in the ER 5. ____ move to Golgi and transported in ____ to cell surface. _____ available for recognition by ______ cell

Answer 36

1. Ubiquitin, proteasome 2. Proteasome; degrades 3. Transporter for Antigen processing (TAP); lumen; ER 4. ER resident aminopeptidase (ERAP), MHC I 5. MHC I + peptide; exocytic vesicle; Antigen MHC I; CD8+ T cell

Question 37

A normal cell displays about ____ loaded MHC I on its cell surface at any one time

Answer 37

100,000

Question 38

Because of ____, different ___ of MHC are displayed at any one time

Answer 38

polymorphism; alleles

Question 39

Why can MHC I on cell surface display samples of all endogenous proteins manufactured

Answer 39

each allele binds to a different peptide

Question 40

MHC class II present only on

Answer 40

APCs

Question 41

MHC II 2 chains

Answer 41

a and B chain

Question 42

MHC II a chain

Answer 42

three domains - extracellular α1 and α2, a transmembrane domain and a cytosolic domain

Question 43

MHC II B chain

Answer 43

three domains - extracellular β1 and β2, a transmembrane domain and a cytosolic domain

Question 44

What chains form peptide binding groove on MHC class II

Answer 44

a1 and B1 chains

Question 45

Peptides binding to MHC II 1. ____ of MHC II molecule is open 2. A peptide of 13-20 aa can be presented, with 9 aa ___ and rest ____ 3. Around __ MHC II alleles must present ___; they are not very ____ 4. They have broad aa requirements based on _____

Answer 45

1. Peptide groove 2. inside groove; protruding on sides 3. 12; all antigens; specific 4. charge, hydrophobicity

Question 46

EXOGENOUS PATHWAY OF MHC II 1. ___ internalizes the antigen via ___ or ___. 2. ____ digest the antigen into short peptides. 3. MHC molecule is synthesized in the _____ 4. _____ of MHC II come together and form a ___. 5. ____ fill the peptide groove while the MHC II is transported through the ___. 6. ____ of the RER fuses with the _____ containing the antigen peptides. 7. The ____ is partially digested leaving a small peptide ____. 8. CLIP is removed by ____, a peptide exchanger molecule, and antigen peptide binds to the ____. 9. MHC II with ____ is transported to membrane and presented.

Answer 46

1. APCs; phagocytosis; endocytosis 2. Lysozomal enzymes 3. RER 4. a and B chains; groove 5. Invariant; golgi 6. Exocytic vesicle; endosomephagolysosome 7. invariant chain; CLIP (class II associate Ii peptide) 8. DM; MHC II groove 9. antigen in groove

Question 47

What is MHC restriction

Answer 47

Only antigen fragments that can bind in the groove of a MHC molecule can trigger an immune response.

Question 48

A foreign molecule that cannot bind to at least one MHC molecule will not

Answer 48

trigger an adaptive immune response

Question 49

What determines susceptibility to infectious and autoimmune diseases

Answer 49

specific MHC alleles

Question 50

MHC heterozygotes are at an advantage because

Answer 50

they can respond to a greater range of antigens

Question 51

Why are there not more than 6 different MHC I and 12 different MHC II in an individual

Answer 51

increases risk that MHC molecules could bind and present more self antigens

Question 52

No single MHC haplotype confers

Answer 52

major survival advantages on individual animals

Question 53

BoLA-Aw7 linked to

Answer 53

resistance to bovine leukosis (bovine leukemia virus)

Question 54

BoLA-A*16 linked to

Answer 54

resistance to mastitis

Question 55

BoLA DR locus linked to

Answer 55

resistance to Dermatophilus sp.

Question 56

ELA-A9 linked to

Answer 56

susceptibility to equine recurrent uveitis

Question 57

ELA-A3, ELA-A15, ELA-Dw13 linked to

Answer 57

development of sarcoid tumors (likely induced by bovine papilloma virus)

Question 58

Class I MHC present endogenous antigens

Answer 58

to CD8+ T cells

Question 59

Class II MHC molecules present exogenous antigens

Answer 59

to CD4+ T cells

Question 60

Class I MHC molecules present ___ antigens

Answer 60

endogenous