MHC structure/fxn/polymorphism & antigen presentation Flashcards Preview

Immuno Block 1 > MHC structure/fxn/polymorphism & antigen presentation > Flashcards

Flashcards in MHC structure/fxn/polymorphism & antigen presentation Deck (68):
1

What is a large cluster of genes that encode specialized host cell glycoproteins?

Major histocompatability complex (MHC)

2

Describe the general function of MHC and how are they related to T cells

some glycoproteins encoded by MHC bind to processed antigens and "present" them on the cell surface

  • peptides presented by MHC can be specifically recognized by T cells

3

Describe the MHC class I molecule

MHC I

a chain (HC) encoded by MHC has 3 domains; a1&2 form binding site for peptides ; a3 spans membrane of host cell

B2-microglobulin=>small covalently associated chain not encoded by MHC & folds to form Ig-like domain to associate with a3 domain of MHC class Ia chain

 

4

T/F Everyone expresses an essentially identical B2-microglobulin

true

5

Describe MHC class II

non-covalent association of 2 polypeptide chains

Both a and B chains are glycosylated transmembrane proteins that have 2 domains

  • a2 & B2 are similar to Ig domains
  • a1 & B1 form a cleft to bind to peptides

 

6

Describe the binding groove of each of the MHC molecules

MHC class I molecules are closed on the ends

MHC class II molecules are open on the ends

7

MHC molecules must be able to bind strongly to a diverse array of peptides that is so strong that it will do what?

bound peptide so tight that it co-purifies with them

8

With peptide binding recognizing general features, what is the most important part of the binding?

binding cleft of MHC have pockets where AA residues have a particular structure can anchor peptide

the sequence of the peptide is not as important as the position of anchor residues 

9

Describe the peptide binding by the MHC class I molecule

  • bind to peptides 8-10 AA long and binding groove is closed on each end
  • stabilized by contacts bw N-terminal and C-terminal ends of peptide and invariant sites found at ends of binding groove
  • peptide lies an elongated conformation along binding groove

10

Describe the binding by MHC class II molecules

  • bind to peptides that are at least 13 residues in length & much longer
  • ends of the MHC class II binding groove is open ended
  • MHC class II molecules accommodate longer peptides

11

What is the degradation of proteins into peptides that can bind to MHC molecules for presentation to T cells?

antigen processing

12

T/F ALL antigens (except peptides) must be processed into pepties before they can presented via MHC molecules

true

13

***Where does antigen processing take place within cells?***

  1. cytosol
  2. endocytic vesicles

14

Describe the antigen processing in the cytosol

  1. antigens derived from pathogens that replicate in cytoplasm of cells are degraded into peptide fragments by a proteosome

 

15

What is a large cylindrical complexes whose fxn is to recycle cytosolic proteins which they enzymatically chop them into small pieces?

proteosome

16

What happens to the peptides that are produced by the proteosome? What complex is needed?

actively transported to the lumen of the ER where they bind to MHC class I molecule

the TAP transporter complex is needed

17

Describe the TAP transporter complex

TAP transporter complex is an ATP-dependent  peptide transporter complex consisting of a TAP1, 2 protein

18

Peptides from foreign proteins bind to what MHC?

MHC class I molecules

 

19

Why are self peptides usually not recognized by patroling CD8 effector cells?

most self-reactive T cells are clonally deleted during the negative selection process in the thymus

only non-self peptides should be recognized by CTLs

20

Where antigens that are phagocytosed confined to? What happens there?

endocytic vesicles 

antigen is degraded by endosomal or lysosomal proteases into peptide fragments

21

antigens that are confined to endosomal compartment are not available for what?

proteosome for processing

22

Where are peptide fragments within endocytic vesicles bind to what and transported where?

bind to MHC class II molecules

MHC:peptide complex is transported to cell surface

23

Peptides generated within endosomal compartments are recognized by what?

recognized by CD4 T cells since they bind to MHC class II molecules

24

What associates with newly synthesized MHC class II molecules and prevents peptides that are in the ER from bindin in the peptide-binding groove of these molecules?

What happens with the new MHC class II: invariant chain complex?

invariant chain

transported to acidified vesicles where the invariant chain is degraded leaving only the clip peptide attached in the binding groove

25

A clip protein is associated with what?

Class II-associated invariant chain peptide

26

Upon interaction with the vesicle membrane protein HLA-DM, the MHC class II molecule does what?

releases clip peptide and then available for binding to peptides within the vesicle

27

What happens if a peptide does not bind in the clef of the MHC class II molecule quickly?

What if it does bind?

the class II molecule will be degraded

complex is stabilized and exported to surface of the cell for antigen presentation

28

Name where intracellular pathogens in ANY cell are processed, bound and presented

  • processed by proteosomes in cytosol of infected cell
  • peptides bind to MHC I and MHC:peptide complex are transported to surface of cell
  • peptides are presented to antigen-specific CD8 T cells

29

Extracellular pathogens (bacteria) are endocytosed by what?

macrophages, dendritic cells, or B cells

30

Name extracellular pathogens are processed, bound, and presented

  • endocytosed antigen processed w/in endocytic vesicles
  • bind to MHC II molecules and MHC:peptide complex is displayed on surface of cell
  • presented to antigen-specific CD4 T cells

31

Extracellular pathogen, pathogen-derived antigen or toxin binds to what?

binds to B cell receptor on an antigen-specific B cell

32

Name where the extracellular pathogen, pathogen-derived pathogen or toxin is processed, bound, presented

  • endocytosed and processed by the B cell
  • bound to MHC II molecules and presented on surface of B cell
  • presented to antigen-specific CD4 T cells

33

T/F MHC I and II are expressed differentially on cells

true

34

MHC class I present peptides derived from what? where? to what?

  • derived from pathogens
  • in the cytosol
  • to either naive or effector CD8 T cells

35

CD8 T cells are programmed to kill any cell that presents what?

their cognate antigen via MHC class I molecules

36

MHC class II molecules present peptides produced by what? to what?

  • produced by processing in endocytic vesicles
  • to either naive or effector CD4 T cells (T helper)

37

Where are MHC class II molecules found?

on antigen presenting cells

38

CD4 T cells are activated by the antigen presenting cells (APC). What is the primary role of these?

to activate other cells of the immune system

39

Other than APCs, where else are MHC II molecules present on? Why is this important?

  • present on thymic cortical epithelial cells
  • important in positive selection of MHC-binding thymocytes durin the thymic maturation process

40

What does the MHC gene complex encode?

  • TAP 1, TAP 2
  • proteosomes
  • variety of cytokines
  • several complement proteins

41

What are teh most polymorphic genes in the mammalian genome?

MHC class I and II

42

***Describe the 2 properties of MHC that make it difficult for pathogens to evade immune responses in this way***

  1. MHC is polygenic but MHC I and II found on chromosome 6
  2. MHC class I and II genes are highly polymorphic (multiple alleles for each isoform)

43

What isoforms are found on MHC class I? Where are they expressed?

HLA-A, HLA-B, HLA-C

all expressed on most cells

44

What are the isoforms of MHC class II? where are they expressed?

HLA-DP, HLA-DQ, HLA-DR

all expressed by most B cells, APCs, thymic epithelial cells

45

T/F MHC class I and II molecules experience NO rearrangement or somatic alterations occur

True

46

Where does the diversity of MHC expression result from?

polygeny(for each individual) and polymorphism (w/in population)

47

What is a naturally occuring variant of a particular gene?

allele

48

What is a different form of a protein that is encoded by the alleles of a gene or by different but closely related genes?

isoform

49

For a linked set of polymorphic genes, the set of alleles carried on a single chromosome 6 is what?

haplotype

50

What are the 6 isoforms of MHC class I? Which are highly polymorphic and what is their function?

  • Highly polymorphic: HLA-A, HLA-B, HLA-C => present peptide antigens to T cells

HLA-E, HLA-F, HLA-G

51

Which MHC I isoforms are oligomorphic and form ligands for NK cell receptors? What immune system is involved?

HLA-E and HLA-G

involved in innate immune responses

52

What isoform is monomorphic and remains intracellular with unknown function?

HLA-F

53

What are the 5 isoforms of MHC II? Which are highly polymorphic? What do they present to?

  1. HLA-DR
  2. HLA-DQ
  3. HLA-DR
  4. HLA-DM
  5. HLA-DO

highly polymorphic cells present them to CD4 T cells

54

Which isoforms of MHC II are oligomorphic and have regulatory roles in peptide loading onto HLA-DP, HLA-DQ, and HLA-DR?

HLA-DM and HLA-DO

55

T/F MHC II molecules are heterodimeric

What are they composed of?

true

composed of an alpha chain and a beta chain

56

Why does a fully heterozygous person express 2 haplotypes of each MHC genes?

each individual expresses both alleles of each HLA gene

57

What is the minimum number of HLA class I isoforms expressed by an individual? maximum?

3 if homozygous at each loci

6 if heterozygous at each loci

58

What is the minimum number of HLA class II isoforms? maximum?

Why is this more complicated?

9 with 3 B chains paired w/ 3 different distinct a chains

48 each a and B chain is heterozygous and HLA-DR B chain is inherited on each chromosome => 8 distinct B chains w/ potential to pair w/ 6 a chains

59

How does the polymorphism affect the peptide binding ability of MHC molecules?

different forms of MHC I and II expressed by different individuals can be highly divergent but still function properly

  • ex: differences bw differnt forms of HLA-A are concentrated in regions of MHC molecule taht binds peptide or binds to TCR molecule => alterations in regions of MHC gives rise to differences in peptide binding characteristics of different form of HLA-A => true for each of MHC I and II

60

Describe transplant rejection

transplanted tissues or organs from donors bearing MHC molecules that differ from those of recipient are reliably rejected

61

What is the rejection of a graft primarily the result of? Describe this action

result of a potent T cell mediated immune response

  • large % of T cells in recipient react specifically w/ particular allogenic (non-self) MHC molecules

62

Describe graft vs host disease

prior to bone marrow transplant-recipient immune system is destroyed

following transplantation, mature T cells from the donor bone marrow attacks recipients tissues

63

A transplant bw genetically identical individuals is called what?

syngeneic transplant or isograft

64

A transplant bw genetically differnet ppl is called what?

allogeneic transplant or an allograft

65

A transplant from one species into a different species is what?

xenograph

66

A transplant of tissue from one area of an individual's body to a different area of the same individual is called what?

autograft

67

T/F T cells ONLY recognize peptides bound to
MHC molecules

true

68

How is peptide binding of MHC I stabilized?

  • contacts between the aminoterminal and carboxyterminal ends of the peptide
  • invariant sites found at the ends of the binding grooves