MHC -Thrush Flashcards

1
Q

What are human leukocyte antigens (HLA)?

A

The same thing as MHC in humans

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2
Q

What are the characteristics of class I MHC?

A

expressed on most nucleated cells
present Ag to CD8+ T cells (ex. Tc, CTL)
HLA-A, HLA-B, and HLA-C in humans

the class I MHC gene encodes for a single chain which when associated with the invariant beta2-microglobulin (NOT on MHC gene) forms the Class I MHC

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3
Q

What are the characteristics of class II MHC?

A

expressed primarily by professional APCs (Macrophages, B cell, DC)
present Ag to CD4+ T cells (ex. Th)
HLA-DP, HLA-DQ, and HLA-DR in humans

are heterodimers coded for by the alpha and beta genes within the MHC locus

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4
Q

What are the characteristics of class III MHC?

A

secreted proteins found in serum
complement proteins, some cytokines (TNF), proteins involved in Ag processing (TAP, LMP2 and LMP7), etc

Not as important in transplant reactions

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5
Q

What 2 features of MHC proteins make them highly polymorphic?

A
  1. co-dominance–> both alleles (maternal and paternal) are expressed for each MHC
  2. MHC genes are polygenic: there are 3 different MHC class I proteins (ex: HLA-A, HLA-B, HLA-C)–> can get 6 different Class I MHC and 12 different class II MHC proteins
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6
Q

Why is it difficult to find a match for organ transplant?

A

Because MHC genes are polymorphic–> there is a lot of variation in out gene sequence and our bodies are able to tell self vs. non-self via the MHC molecules

significant differences in MHC will lead to the immune system attempting to destroy the foreign tissue.

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7
Q

What is a haplotype?

A

The full complement of genes that an individual has (ex: Alleles for HLA-A, B, C, DR, DQ, DP coming from the maternal side would be considered one haplotype)

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8
Q

What is the structure of class I MHC proteins? What T cell binds to them and what domain makes up the binding cleft?

A

a heterodimer of three alpha chains (alpha1, alpha2, and alpha3) associated with an invariant beta2-microglobulin

-beta2-microglobulin is structurally similar to alpha3

  • alpha1 and alpha2 form the peptide binding cleft
  • ->holds 8-10 a.a. peptide (pita model) –> anchor residues are a the ends
  • -> where most polymorphisms are located

-alpha3 is highly conserved and interacts with CD8

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9
Q

What is the structure of Class II MHC proteins? What T cell binds to them and what domain makes up the binding cleft?

A

Heterodimer of alpha and beta chains
–>encoded for by different genes

protein divided into: alpha1/alpha2 and beta1/beta2

alpha1/beta1 is the Ag binding cleft

CD4 contacts alpha2/beta2 area

accommodates 18-20 amino acids: hot dog model
–> anchor residues can be anywhere in the peptide

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10
Q

How is MHC different from antibodies?

A

MHC can bind to a variety of different antigenic peptides, where antibodies can only bind to one antigen

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11
Q

Which class of MHC displays endogenous peptides? What cell recognizes them? What is the preferred length of endogenous peptide?

A
class I MHC --> to be recognized by CD8+ T cells
(ex: viral antigens that come from within the cell) 

Nonamers are the preferred length of peptide

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12
Q

Which class of MHC displays exogenous peptides? What cell recognizes them?

A

Class II MHC –> recognized by CD4+ T cells

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13
Q

What class MHC proteins are found on the “professional” antigen presenting cells?

A

MHC class II proteins are presented on dendritic cells, macrophages, and B cells.

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14
Q

Which cells don’t normally express class II MHCs but can be induced to express them?

A

human T cells

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15
Q

What will individuals with defects in expression of the class II transactivator (CIITA) exhibit? What is this syndrome called?

A
Defects in CIITA would not allow for the expression of class II MHC protein. 
Without these molecules, T helper cells would not be activated--> the individual would have defects in immune system activity

This is called “bare lymphocyte syndrome”.

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16
Q

How are endogenous antigens processed and paired with an MHC? What will recognize this mature Ag-MHC complex?

A
  • Endogenous Ags are tagged with ubiquitin for degradation by the proteosome
  • LMP2 and LMP7 are the enzymes that associate with the proteosome to cut protein near the hydrophobic residues (class I anchors)
  • degraded proteins are transported by TAP (transporter associated with Ag Processing) to the rough ER where it joins a class I MHC peptide before traveling to the golgi and the cell surface to become a membrane bound protein

will be recognized by the TCR of CD8+ T cells

17
Q

How are these exogenous peptides degraded?

A

exogenous peptides are degraded by the endocytic pathway (brought into macrophages or DCs via endocytosis and then degraded by the lysosome before joining MHC class I molecules)

18
Q

How are exogenous peptides brought into the cell and processed to be paired with and MHC?

A
  • Macrophages, DCs or B cells bring in exogenous Ags into an endocytic vesicle (phagosome)
  • after fusion of endosome with lysosome (low pH), the protein will be degraded
  • ->yields peptides of ~13-20a.a. long

-Newly made MHC class II are produced in the rough ER. Invariant chain (Ii) associates with newly made class II (preventing it from binding to peptides)
-As the MHC II travels to the surface, the Ii is partially degraded to yield CLIP
(class II associated invariant polypeptide)
-once CLIP and MHC class II reach the phagolysosome, then the CLIP is removed and the antigenic peptide can associate with MHC class II
-HLA-DM – binds to class II and releases CLIP when Ag peptide is binding

19
Q

What do gamma delta TCRs use instead of MHC and why? What other cells can use a similar system?

A

-they can recognize non-protein antigens
-Use CD1 molecules instead of MHC
associates with beta2-microglobulin
-CD1 genes on chromosome #1 (not within MHC locus)
-expressed on professional and non-professional APCs, B cells, thymocytes, epithelial cells
-5 different types of CD1
-expression depends on the type/class of CD1
-lipids from M. tuberculosis and M. leprae found to be presented with CD1

-NK cells may also recognize Ag with CD1 (even though they are not antigen specific)

20
Q

Why would we use B cells as antigen presenting cells when DCs and macrophages are great APCs?

A

Because in low antigen concentrations, the antigen might not be presented enough on the DC and macrophage surfaces to illicit a T cell response

B cells can increase the concentration of antigens to cause an immune response