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

MHC structure/fxn/polymorphism & antigen presentation Flashcards

1
Q

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

A

Major histocompatability complex (MHC)

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2
Q

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

A

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
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3
Q

Describe the MHC class I molecule

A

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

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4
Q

T/F Everyone expresses an essentially identical B2-microglobulin

A

true

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5
Q

Describe MHC class II

A

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
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6
Q

Describe the binding groove of each of the MHC molecules

A

MHC class I molecules are closed on the ends

MHC class II molecules are open on the ends

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7
Q

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

A

bound peptide so tight that it co-purifies with them

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8
Q

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

A

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 **

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9
Q

Describe the peptide binding by the MHC class I molecule

A
  • 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
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10
Q

Describe the binding by MHC class II molecules

A
  • 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
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11
Q

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

A

antigen processing

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12
Q

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

A

true

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13
Q

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

A
  1. cytosol
  2. endocytic vesicles
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14
Q

Describe the antigen processing in the cytosol

A
  1. antigens derived from pathogens that replicate in cytoplasm of cells are degraded into peptide fragments by a proteosome
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15
Q

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

A

proteosome

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16
Q

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

A

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

the TAP transporter complex is needed

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17
Q

Describe the TAP transporter complex

A

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

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18
Q

Peptides from foreign proteins bind to what MHC?

A

MHC class I molecules

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19
Q

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

A

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

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20
Q

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

A

endocytic vesicles

antigen is degraded by endosomal or lysosomal proteases into peptide fragments

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21
Q

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

A

proteosome for processing

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22
Q

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

A

bind to MHC class II molecules

MHC:peptide complex is transported to cell surface

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23
Q

Peptides generated within endosomal compartments are recognized by what?

A

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

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24
Q

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?

A

invariant chain

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

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25
Q

A clip protein is associated with what?

A

Class II-associated invariant chain peptide

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26
Q

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

A

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

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27
Q

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

What if it does bind?

A

the class II molecule will be degraded

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

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28
Q

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

A
  • 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
Q

Extracellular pathogens (bacteria) are endocytosed by what?

A

macrophages, dendritic cells, or B cells

30
Q

Name extracellular pathogens are processed, bound, and presented

A
  • 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
Q

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

A

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

32
Q

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

A
  • 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
Q

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

A

true

34
Q

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

A
  • derived from pathogens
  • in the cytosol
  • to either naive or effector CD8 T cells
35
Q

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

A

their cognate antigen via MHC class I molecules

36
Q

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

A
  • produced by processing in endocytic vesicles
  • to either naive or effector CD4 T cells (T helper)
37
Q

Where are MHC class II molecules found?

A

on antigen presenting cells

38
Q

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

A

to activate other cells of the immune system

39
Q

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

A
  • present on thymic cortical epithelial cells
  • important in positive selection of MHC-binding thymocytes durin the thymic maturation process
40
Q

What does the MHC gene complex encode?

A
  • TAP 1, TAP 2
  • proteosomes
  • variety of cytokines
  • several complement proteins
41
Q

What are teh most polymorphic genes in the mammalian genome?

A

MHC class I and II

42
Q

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

A
  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
Q

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

A

HLA-A, HLA-B, HLA-C

all expressed on most cells

44
Q

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

A

HLA-DP, HLA-DQ, HLA-DR

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

45
Q

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

A

True

46
Q

Where does the diversity of MHC expression result from?

A

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

47
Q

What is a naturally occuring variant of a particular gene?

A

allele

48
Q

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

A

isoform

49
Q

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

A

haplotype

50
Q

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

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

HLA-E, HLA-F, HLA-G

51
Q

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

A

HLA-E and HLA-G

involved in innate immune responses

52
Q

What isoform is monomorphic and remains intracellular with unknown function?

A

HLA-F

53
Q

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

A
  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
Q

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

A

HLA-DM and HLA-DO

55
Q

T/F MHC II molecules are heterodimeric

What are they composed of?

A

true

composed of an alpha chain and a beta chain

56
Q

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

A

each individual expresses both alleles of each HLA gene

57
Q

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

A

3 if homozygous at each loci

6 if heterozygous at each loci

58
Q

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

Why is this more complicated?

A

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
Q

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

A

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
Q

Describe transplant rejection

A

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

61
Q

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

A

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
Q

Describe graft vs host disease

A

prior to bone marrow transplant-recipient immune system is destroyed

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

63
Q

A transplant bw genetically identical individuals is called what?

A

syngeneic transplant or isograft

64
Q

A transplant bw genetically differnet ppl is called what?

A

allogeneic transplant or an allograft

65
Q

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

A

xenograph

66
Q

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

A

autograft

67
Q

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

A

true

68
Q

How is peptide binding of MHC I stabilized?

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

Immuno Block 1 (14 decks)

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