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IP > Antigen Processing and MHC > Flashcards

Antigen Processing and MHC Flashcards

1
Q

What the T cell receptor gene rearrangement? what are they recognized by? recombination?

A
  • recombination signal sequences (RSS) flanking V, D, J germline sequences are recognized by proteins encoded by recombination activating genes (RAGs) -expressed in T lymphocytes -recombine V region with J region or D with J recognition of 12 base with 23 base spacers in gremlin sequence
  • alpha chain TCR: V-J arrangement
  • beta chain TCR: D-J recombination followed by V-DJ recombination
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2
Q

How to recognize antigen in T cells? Signal complex?

A
  • TCR -complex with CD3 (5 molecules together) -signal transduction
  • CD 4 (MHC 2) or CD 8 (MHC 1) -bind with MHC from antigen presenting cell
  • antigen sits in binding cleft of MHC -to stabilize and send signal to nucleus
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3
Q

What are the two classes of T cells?

A
  • alpha and beta chain (more often)
  • gamma and delta chain (5-8%)
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4
Q

Where are gamma and delta chain T cells found (specific tissues)?

A
  • reproductive tract
  • certain regions of digestive tract
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5
Q

Segments in T cell receptors?

A

alpha: V, J
beta: V, D, J

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6
Q

Which as more diversity, Ig or T cells?

A

T cells

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7
Q

How many T cells make it through the education to be a T cell? two processes?

A

maybe 5%

  • does it work?
  • does it recognize self vs non self?
  • low success rate
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8
Q

How do CD8-T cells function?

A
  • CD8 (MHC 1), TCR, CD3 (intracellular signal)
  • identifies antigen and engages
  • kills cell
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9
Q

How do CD4-T cells function with macrophages?

A
  • macrophage is infected
  • moves to TCR, CD4, CD3
  • activate macrophage
  • lysosomes (reactive O2) destroy internal organism
  • phagosomes/lysosomes fused together
  • destroys antigen
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10
Q

How do CD4-T cells function with B cells?

A
  • MHC class II on B cell
  • antigen presented to CD 4 cells
  • cytokines activate B cell to produce antibodies
  • class switching
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11
Q

Difference in structure between MHC 1 and 2?

A

MHC 1- only alpha chains (1, 2, 3), beta 2 micro globulin

MHC 2- alpha chain (1, 2) and beta chain (1, 2) - size of amino acid that can be presented is different

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12
Q

What MHC does CD 8 (cytotoxic) bind to?

A

alpha 3 domain of MHC class 1

-endogenous (produced in cell)

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13
Q

What MHC does CD 4 (helper) bind to?

A

beta 2 domain of MHC class 2

-exogenous (outside of cell)

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14
Q

What is the target pathogens of MHC 1 vs 2?

A

1- endogenous (produced in cell- not supposed to be there)

2- exogenous (foreign object- T cells learn what is self)

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15
Q

Peptide binding in MHC 1 (HLA-A2 human)? MHC 2 (HLA-DR1)?

A

MHC 1

  • variable
  • shorter fragment than can be accommodated in binding cleft

MHC 2

  • longer fragment
  • can accommodate more diversity
  • once made, MHC cannot vary
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16
Q

What determines how long an antigen can be in MHC?

A

peptide binding grooves

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17
Q

What is HLA?

A

human leukocyte antigen (human MHC class isotopes)

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18
Q

How many HLA class 1 isotopes? class2?

A

class 1: 6

class 2: 5

19
Q

What type of expression does MHC (HLA) display?

A

codominant

-one HLA-A from mom and one from dad, you will express two, one of each

20
Q

What are the properties of HLA class 1 isotopes?

A

A, B, C- polymorphic, highly diverse, heterogeneity, this is how we see diversity in micro organisms, our body needs to match these one- more difficult

E,F,G- less diversity, oligopmorphic, monomorphic

21
Q

What are the properties of HLA class two?

A

DP, DQ, DR (highly)- polymorphic, hundreds of allotypes

DM, DO- oligomorphic, monomorphic

22
Q

General properties of MHC (HLA) proteins? difference from other immunoglobulins? diversity?

A
  • members of immunogolubulin superfamily of proteins
  • unlike immunoglobulins (TCR), these are encoded by conventional, stable genes that do not rearrange of undergo any somatic or developmental change
  • inherited diversity- gene families, genetic polymorphism
  • isoforms
  • two classes (1, 2)
23
Q

Gene families?

A

consisting of multiple, similar genes encoding MHC proteins

24
Q

Genetic polymorphism? how many different alleles can be expressed? tissue matching?

A
  • the presence, within the population of multiple, alternative forms or alleles of a gene
  • allotypes- encoded proteins, hundreds of them
  • makes tissue matching between unrelated people unlikely
  • up to 12 expressed
25
Q

Isoform?

A
  • denotes a particular MHC protein
  • used because of the diversity that arises from the combination of multiple genes and alleles from the diversity of MHC class 1 and 2
  • each MHC protein expressed on the cell surface is an isoform
26
Q

Highly polymorphic?

A
  • certain MHC class 1 and 2 genes have many different alleles and proteins encoded
  • more polymorphic involved in antigen presentation
27
Q

monomorphic? oligomorphic?

A
  • mono: no polymorphism
  • oligo: only a few alleles
28
Q

What chromosome is human MHC on? how is it inherited? rate of recombination?

A
  • chromosome 6
  • inherited as a unit or haplotype
  • rate of recombination is low, recombination could be detrimental
29
Q

what is a haplotype?

A
  • linked cluster of polymorphic genes, sets of alleles carried on a single chromosome
  • every person inherits two, one from each parent
30
Q

Tissue distribution of MHC (class 1 vs 2)?

A

class 1:

  • all nucleated cells in the body
  • express multiple copies
  • constitutively expressed, basal level
  • particular cytokines trigger higher level of expression on surface, greater immune surveillance

class 2:

  • some activated T cells
  • B cells
  • macrophages/APC
  • thymic epithelial cells
31
Q

What creates the walls of the peptide binding cleft (MHC class 1)? floor?

A
  • walls:alpha helices 1 and 2
  • floor: beta pleated sheet
  • peptide anchored at both ends
32
Q

How does the peptide interact with the peptide binding cleft?

A

hydrogen bonds

33
Q

What is the difference between MHC class 1 and class 2 binding cleft? affect?

A
  • MHC class 2 has an alpha helix and beta sheet that make up the wall of the binding cleft, can accommodate a bigger peptide
  • affect peptide binding and T cell interactions
34
Q

MHC restriction?

A
  • T cells recognize processed peptide antigen presented by products of the MHC locus
  • within a given individual, each clone of T cells recognize peptides only in the context of that individuals MHC molecules
35
Q

CTL (CD8+) recognize what class of MHC? Helper T cells (CD4+)?

A

CD8- class 1

CD4- class 2

36
Q

Size of peptides for MHC class 1? class 2? endogenous or exogenous?

A

class 1

  • 8-10 amino acids b/c anchored at both ends
  • endogenous for presentation to CD8+

class 2

  • up to 25 amino acids
  • exogenous for presentation to CD4+
  • extracellular foreign protein
  • can bind self peptides
37
Q

Exogenous antigen processing?

A
  1. extracellular particles are taken up by phagocytosis in to an endocytotic vesicle (endosome) or phagosome: -extracellular bacteria -extracellular virus particles -soluble protein antigens
  2. membrane bound vesicles travel inward, they become acidified (by membrane associated proton pumps)
  3. can fuse with other vesicles such as lysosomes to become phagolysosomes -lysosomes contain hydrolyses and proteases -result in protein degradation and formation of peptides
  4. biosynthesis and transport of class 2 MHC molecules to endosomes -invariant chain and CLIP (sits in binding cleft and holds open) -chaperonin maintains proper conformation of MHC 2 -buds from ER into Golgi, transports
  5. exocytic vesicle containing MHC 2 fuses with phagosomes containing antigen -partially cleave invariant, leaving CLIP -removed CLIP from MHC 2 -HLA-DM receives CLIP, recycled
  6. MHC 2 receives peptide carries it to CD4+
38
Q

What is the role of CLIP?

A

holds conformation of binding cleft of MHC 2

39
Q

Endogenous antigen processing?

A
  1. virus in cytoplasm
  2. production of proteins in cytosol
  3. load into proteasome
  4. moved into ER via TAP
  5. chaperonins (calnexin) associate transport through ER membrane
  6. beta 2 microglobulin binds, calnexin dissociates
  7. beta microglobulin/class 1 complex binds to another complex containing calreticulin and tapasin (stability)
  8. load peptide into MHC class 1
  9. move to golgi
  10. move as exoctytoic vesicle to CD8+
40
Q

proteasome processing and infection. constitutive proteasome? what do cytokines do in response to infection? what does IFN-gamma do in response to cytokine?

A
  • proteasome: 28 subunit cylindrical protease complex
  • degrades protein into peptide -peptides transported to ER by TAP (heterodimer TAP1, TAP2)
  • constitutive- made up of multiple subunits, under normal conditions
  • cytokines alter subunits in newly synthesized proteasome forming immunoproteasome IFN-gamma
  • increases number of proteaseomes
  • alters subunits making up proteasome which results in altered enzyme activity that:
  • increases cleavage after hydrophobic residues
  • decreased cleavage after acidic residues
41
Q

Cross presentation?

A
  1. exogenous antigen for loading into MHC 2 -some goes into class 2 path, some slips into class 1
  2. proteolytic digestion
  3. release some into cytoplasm
  4. MHC 1 path
  5. this primes CD8+ cells
42
Q

T cell clones stimulation?

A

antigen processing and presentation stimulates T cell clones recognizing particular antigens which will become effector T cells

43
Q

What MHC does dendritic cells express?

A

both 1 and 2

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