4. Antigen Processing and Presentation Flashcards

1
Q

What is MHC restriction?

A
  • T cell co-recognition of a foreign peptide/ self MHC molecule
    > particular MHC allele restricts ability of T cells to recognize antigens
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2
Q

Cytosolic pathogens bind to what MHC class?

A

MHC class I
- present antigen to effector CD8 T cells

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3
Q

Intravesicular pathogens bind to what MHC class?

A

MHC class II
- present antigen to effector CD4 T cells

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4
Q

Extracellular pathogens bind to what MHC class?

A

MHC class II
- present antigen to effector CD4 T cells
> activation of B cells to secrete Ig to eliminate extracellular pathogens

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5
Q

How can extracellular antigens be displayed on MHC I?

(normally on MHC class II)

A
  • cross-presentation of extracellular antigens on MHC class I molecules by DCs

> translocation of proteins from phagolysosome > cytosol for degradation by proteasome > resultant peptides passed into ER where they load onto MHC I

> direct transport of antigens from phagolysosome > vesicular loading compartment where they load onto MHC I (no passage through cytosol)

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6
Q

How can extracellular antigens be cross-presented on MHC class I molecules by DCs?

A
  • translocation of proteins from phagolysosome > cytosol for degradation by proteasome > resultant peptides passed into ER where they load onto MHC I
  • direct transport of antigens from phagolysosome > vesicular loading compartment where they load onto MHC I (no passage through cytosol)
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7
Q

How can cytosolic antigens be displayed on MHC class II?

(normally on MHC class I)

A
  • autophagy pathways can deliver cytosolic antigens for presentation by MHC class II molecules
  • portions of cytoplasm are taken into autophagosomes
    > specialized vesicles fused with endocytic vesicles/ lysosomes
  • contents catabolized > peptides can be bound to MHC II
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8
Q

What cells express MHC class I molecules?

A
  • all nucleated cells
  • not RBCs (unnucleated)
  • most highly expressed in hematopoietic cells
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9
Q

What kind of protein is MHC molecule?

A
  • member of immunoglobulin superfamily
    > has immunoglobulin domains
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10
Q

Where is the peptide-binding groove formed in both MHC class I/ MHC class II molecules?

A
  • by the membrane-distal domains
  • MHC class I > α1/ α2 domains
  • MHC class II > α1/ β1 domains
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11
Q

Where is the immunoglobulin domain structure in MHC class I/ MHC class II molecules?

A
  • in the membrane-proximal domains
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12
Q

How are peptides bound differently in MHC class I/ II?

A
  • MHC class I > peptide bound in elongated conformation/ both ends tightly bound at either end of the cleft (closed at both ends)
  • MHC class II > peptide bound in elongated conformation/ ends of peptide not tightly bound > peptide extends beyond cleft (open at both ends)
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13
Q

What are the structural characteristics of MHC class I?

  • present antigens to CD8+ T cells
A
  • composed of 4 domains: α1/ α2/ α3/ β2 microglobulin
  • α3/ β2 microglobulin > proximal/ fold similar to Igs
  • α1/ α2 domains > antigen binding groove/ highly polymorphic
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14
Q

What are the structural characteristics of MHC class II?

  • present primarily on APCs > present antigens to CD4+ T cells
A
  • composed of 2 separate chains: α/ β
  • each MHC II chain is folded into 2 domains > α1 and α2/ β1 and β2
  • α1/ β1 domains form antigen binding groove
  • β chain is polymorphic (especially β1 domain)
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15
Q

How do MHC class I molecules interact with peptides?
> bound by their ends

A
  • series of hydrogen bonds/ ionic interactions at each end
  • AA that form these bonds are common to all MHC class I molecules
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16
Q

How do peptides bind to MHC class I molecules?

A
  • through structurally related anchor residues
  • anchor residues differ for peptides that bind different alleles of MHC class I
  • anchor residues are similar for all peptides that bind to same MHC molecule
  • anchor residues that bind a particular MHC do not have to be identical but are always related (same chemical features)
  • peptides also bind MHC I through amino/ carboxyl termini
17
Q

What are anchor residues?

A
  • AA’s in peptides that interact with MHC molecule
  • anchor residues differ for peptides that bind different alleles of MHC class I
  • anchor residues are similar for all peptides that bind to same MHC molecule
  • anchor residues that bind a particular MHC do not have to be identical but are always related (same chemical features)
18
Q

How long are peptides that bind to MHC 1?

A
  • 8-10 AA
  • have 2/3 anchor residues
19
Q

How long are peptides that bind to MHC II?

A
  • variable length of peptides (13-18 AA residues)
  • have 4 anchor residues
  • naming convention > first anchor residue is residue 1
20
Q

How do peptides bind to MHC class II molecules?

A
  • series of hydrogen bonds distributed along length of protein in the binding groove
21
Q

What is MHC called in humans/ mice?

A
  • humans > HLA
  • mice > H2
22
Q

What were MHC antigens called when first discovered?

A

histocompatibility antigens

23
Q

What are the different human MHC I/ MHC II molecules? (HLA)

A
  • MHC I > A/ B/ C
  • MHC II > DP/ DQ/ DR
24
Q

What are the different mice MHC I/ MHC II molecules? (H2)

A
  • MHC I > K/ D
  • MHC II > A/ E
25
Q

What is polygeny?

A
  • MHC region contains multiple genetic loci encoding proteins with the same function
  • ensures that each individual produces different MHC molecules
    > ex- HLA-A/B/C can all present peptides to CD8+ T cells
    > ex- HLA-DP/DQ/DR can all present peptides to CD4+ T cells
26
Q

What is polymorphism?

A
  • each gene in MHC locus has several alleles within population
    > ensures diversity in MHC gene expression in population as a whole
27
Q

What is co-dominant expression?

A
  • alleles from each haplotype are expressed in any 1 individual
    > ex- AB blood type/ MHC molecules
28
Q

What contributes to the diversity of MHC molecules expressed by an individual/ population?

A
  • polygeny > presence of different related genes with similar functions > ensures each individual produces a # of different MHC molecules
  • polymorphism > polymorphism of MHC genes ensures diversity in MHC gene expression in the population
29
Q

Where does allelic variation of MHC molecules predominantly occur?

A
  • within peptide-binding region
30
Q

How are MHC molecules co-dominantly expressed?

A
  • genes within MHC locus have codominant expression
    > both maternal/ paternal gene products expressed at same time
31
Q

Where does assembly/ stabilization of MHC class I molecules occur?

A

RER
- TAP (transporter associated with antigen processing) transports peptides from cytosol > RER to associate with MHC class I

32
Q

What is the endogenous pathway for antigen presentation by MHC class I molecules?

A
  • endogenous antigens in cytosol degraded by proteasome > converts protein into smaller peptides
  • peptide transported to RER via TAP
  • MHC I binds to peptide > MHC I-peptide complex transported from RER to plasma membrane
33
Q

What is the exogenous pathway for antigen presentation by MHC class II molecules?

A
  • receptor-mediated endocytosis of extracellular antigens
  • extracellular antigens engulfed into endocytic compartments > degraded by acidic pH lysosomal/ endosomal enzymes
  • peptide associates with MHC class II in endocytic compartment
    > MHC II-peptide complex transported to plasma membrane
34
Q

What is cross-presentation?

A
  • dendritic cells cross-present exogenous antigen via MHC I
    > critical for activation of naive CD8+ T cells
35
Q

What are superantigens?

A
  • antigens recognized by T cells without being processed into peptides captured by MHC molecules
  • produced by many different pathogens
  • responses they provoke are helpful to pathogen
    > systemic toxicity/ suppression of adaptive immune response
36
Q

What is the determinant selection model?

A
  • different MHC class II molecules differ in ability to bind particular processed antigens
    > some peptides may be more critical to eliminate pathogens than others
    > ability of organism to present these peptides would give them an advantage
37
Q

What is the holes in the repertoire model?

A
  • T cells with receptors that recognize certain foreign antigens that closely resemble self-antigens may be eliminated during T cell development > leaves organism without these receptors