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Immunology Jenny > 5. Antigen, antigen presentation and MHCs > Flashcards

5. Antigen, antigen presentation and MHCs Flashcards

1
Q

MHC abbreviation + definition

A

Major histocompatibility complex

“Immunogenic alloantigen proteins on cell surface”

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2
Q

MHC-restricted recognition

A

T cell must interact with both the MHC molecule and the foreign peptide (co-recognition)

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3
Q

MHC’s central role

A

Antigen presentation

  • Genetically determined HLA molecules
  • MHC I: HLA-A, -B, -C (present endogenous Ag’s)
  • MHC II: HLA-DP, -DR, -DQ (exogenous Ag’s)
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4
Q

Genetics MHC

A
  • MHC I and MHC II loci closely linked
  • Polygenic (HLA-A etc)
  • Polymorphic (each locus has many diff. alleles)
  • Co-dominantly inherited (both alleles of gene expressed)
  • MHC III genregion lies between MHC I and II genregions, and codes for complement C3 convertases
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5
Q

Genes of MHC I

A

HLA-A
HLA-B
HLA-C

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6
Q

Genes of MHC II

A

HLA-DP
HLA-DQ
HLA-DR

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7
Q

Combination of MHC polygeny and polymorphism

A
  • Gives several different genes with similar function
  • > individual produces a number of different MHC molecules
  • Gives diversity within individual and population
  • A single cell can display a large array of MHCs
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8
Q

RBC MHC class

A

No MHC, because no nucleus

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9
Q

MHC I structure

A
  • Fixed pocket
  • 8-9 AAs
  • ENDOGENOUS peptide (virus, self, ic parasite, tumor)
  • On all nucleated cells
  • α1-3, β2microglobulin subunits
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10
Q

MHC II structure

A
  • Open cleft
  • 11-25 AAs
  • EXOGENOUS peptide (bacteria, lysosomal invaders)
  • On antigen-presenting cells
  • α1-2, β1-2 subunits
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11
Q

Two main pathways of recieving antigens

A

1) Cytosol-derived (endogenous Ag’s)

2) Endosome/lysosome-derived (exogenous Ag’s)

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12
Q

Where to find pathogens w/products in cell

A
  • Cytosol (MHC I)

- Vesicles (MHC II)

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13
Q

MHC+peptide

A
  • Always appear together on cell surface
  • Firm connection
  • Both created and connected inside cell
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14
Q

MHC synthesis location

A

RER (synthesized by ribosomes)

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15
Q

Cuts pathogenic protein to peptide fragments

Where it cleaves

A

Proteosome

Cleaves next to hydrophobic and basic AAs

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16
Q

Site of connection between MHC I and peptide

Fate of connected complex

A

RER

- Sent to golgi -> exocytosis to cell surface

17
Q

TAP

A

“Transporter associated with antigen processing”

  • ATP-dependent peptide transport
  • Selectivity: prefer >8 AA hydrophobic peptide with carboxyl ends
  • Heterodimer: TAP-1 and -2
  • Transports cytosolic peptide to RER for connection with MHC I
18
Q

Steps and location of endogenous processing

A

Every nucleated cells (MHC I)

1) Cytosolic antigens (viral, self, tumor etc)
2) Cleaved to peptides by proteosome
3) TAP inserts peptides into RER
4) Peptide+MHC I makes complex (chaperone used to cover binding site of MHC I, but has now disappeared)
5) Peptide-MHC-complex travels->golgi->exocytosis to surface of cell (to be recognized by cytotoxic T cells)

19
Q

Non-classical HLA molecules

A

HLA-E, -F, -G

  • Less polymorphic
  • Modulatory effects (e.g recognized by NKG2A inhibitory effector of NK cells)
20
Q

MHC II + exogenous peptide (steps of exogenous processing)

A

On antigen presenting cells (APCs)

1a) Exogenous peptide endocytosed into cell -> endosome
1b) MHC II synthesized in RER (connected to Ii chaperone) -> golgi -> lysosome (acidic -> degrade Ii -> CLIP - sitting in binding seat)
2) Fusion of endosome+lysosome
3) Degradation of pathogenic protein because acidic environment (lysosome)
- CLIP prevents formed peptides from binding MHC II
4) HLA-DM (RER->golgi->fuse with endosome+lysosome) will interact and release CLIP -> peptide can bind
5) Exocytosis of MHC II-peptide complex (not HLA-DM), displayed to Th cells

21
Q

Uptake of exogenous antigens (receptors)

A
  • Phagocytes, DC, thymic epth. cells: any antigens (Lectin-R, Fc γ-R, complement R)
  • B-cells: selected antigens (BCR)
22
Q

Ii

A

“Invariant chain” (chaperone)

  • Prevent self peptide-MHC II binding
  • Stabilizes + targets MHC II into lysosome
  • Cleaved to CLIP in acidic environment
23
Q

CLIP

A

“Class II associated invariant chain peptide”

  • Bound to groove of MHC II molecule
  • Separated when HLA-DM arrives
24
Q

Goal of antigen presentation by different APCs

A

1) Dendritic cell
- To lymph node
- Present to naive T cell
- For priming: induce activation and determine differentiation way of T cell
2) B cells, macrophages
- Present to effector T cell
- Wants to get signals to facilitate their own maturation

25
Q

Cross-presentation of exogenous** antigens

A

Usually by DCs

  • Degraded in cytosol by retrotranslocation**
  • Bind to MHC I
  • Presented to naive CD8 T cells**
  • Activates CD8 T cell
    • Exogenous Ag’s are presented by endogenous pathway (in addition to exogenous pathway?)
    • Needed to generate cytotoxic response to some viral/tumor Ag’s
26
Q

Example of cross-presentation of exogenous Ag’s

A

Viruses/tumors that do not appear in lymph nodes

  • Taken up as exogenous Ag’s
  • Must be presented as endogenous Ag’s for cytotoxic response
  • This is cross-presentation by DCs
27
Q

Cross-dressing of exogenous Ag’s

A

Transfer of preformed peptide-MHC I complexes from infected cells to uninfected APCs without further processing needed
- Transfer via trogocytosis or exosomes

28
Q

Special forms of Ag presentation

A

1) Cross-presentation
2) Cross-dressing
3) CD1-mediated presentation of lipid antigens to T-cells
4) Forcing incorrect Ag presentation by superantigens

29
Q

CD1-mediated presentation of (amphipathic) lipid antigens to T-cells

A
  • CD1 structure similar to MHC I
  • CD1 groove larger, deeper, more hydrophobic
  • Lipid “legs” of Ag deeply inserted into groove -> more hydrophilic portions of ligand are exposed to TCR
  • Many diff. T cells bind these complexes
30
Q

DC roles in Ag processing and presentation

A
  • Classical
  • Cross presentation
  • Cross dressing
  • Lipid presentation
31
Q

Forcing incorrect Ag presentation by superantigens

A
  • Crossbridge between TCR β chain and MHC molecules without being processed
    -> Non-specific activation of T cells
    -> Polyclonal acivation (many diff T cells prod.)
    = weak, non-specific immune reaction to pathogen
    = and massive prod. of cytokines->systemic toxicity
32
Q

Example of diseases with HLA alleles

A 
Mainly autoimmune diseases
- Gluten-sensitive enteropathy
- Narcolepsy
- Psoriasis
- Type I diabetes mellitus
\++
33
Q

Individual MHC allele polymorphism predicts:

A
  • Resistance and susceptibility to infectious and autoimmune diseases
  • Compatibility of tissue transplants
  • Spontaneous abortion
  • Odour and mating preferences

Immunology Jenny (16 decks)

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