Iid - Antigen Exposure, Processing And Presentation

Front 1

Describe the structure of MHC class I molecules

Back 1

Two polypeptide chains:

Heavy chain - three external immunoglobulin-like domains termed alpha 1, alpha 2, and alpha 3 followed by a transmembrane domain and a short cytoplasmic tail.

Beta2 microglobulin - one immunoglobulin-like domain non-covalently associated with the heavy chain

The peptide binding groove is at the interface of alpha 1 and alpha 2 domains; binds peptides that are generally from 8-11 amino acids in length - this length requirement is strict as the peptide binding groove is closed at both ends

Front 2

Describe the synthesis and transport of MHC class I molecules

Back 2

MHC class I molecules are translated as they are translocated into the ER.

When peptide is aquired, the heavy chain/Beta 2 microglobulin/peptide complex is released from the ER and travels to the surface for inspection by the T cell population.

Front 3

What is the function of TAP?

Back 3

Transporter associated with Antigen Processing

Transports peptides from the cytosol to the ER where MHC class I complex is waiting.

Front 4

What is the function of ERAAP?

Back 4

ER-Associated AminoPeptidase

Peptides that are too long to fit into the class I groove can be trimmed within the ER to the appropriate length by this enzyme.

Front 5

In infected cells, are the peptides displayed only foreign peptides?

Back 5

No, they are a mixture of foreign and self

Front 6

Describe the structure of MHC class II molecules

Back 6

Composed of alpha and beta chains of roughly the same size; both have transmembrane portions

The peptide binding groove - between the alpha 1 and beta 1 domains; open at both ends, which means large molecules are capable of binding as long as the part that binds to the class II molecule is unfolded.

Front 7

What is the invariant chain? Why is it important?

Back 7

Newly synthesized class II heterodimers associate in the ER with the invariant chain polypeptide.

It allows class II to complete its folding, prevents class II molecules from binding peptides in the ER, and directs class II molecules that have been released from the ER to endosomes rather than the cell surface.

Front 8

Describe antigen processing for MHC class II molecules

Back 8

Class II molecules are loaded with peptides within the endocytic compartment (which includes endosomes and lysosomes).

Due to low pH in endosomes and lysosomes, the invariant chain is digested leaving a small piece called CLIP.

CLIP is removed from the class II groove by HLA-DM and is replaced by a peptide (generally 12-17 amino acids in length.

Loaded class II molecules are then taken to the cell surface.

Front 9

Where do the CD8 and CD4 receptors bind on MHC molecules?

Back 9

CD8 binds to the side of the class I molecule alpha 3 domain.

CD4 binds to the side of the clas I molecule beta 2 domain.

Front 10

What can cause MHC class II molecules to be upregulated on B cells, macrophges, and dendritic cells, and can cause MHC class II expression on cells that are usually MHC class II negative?

Back 10

Interferon gamma

Front 11

What causes dendritic cells to mature?

Back 11

TLR signaling and production of TNF and IL-1 among others

Front 12

What is cross presentation?

Back 12

A mechanism by which a dendritic cell displays the antigens of another cell and activates a naive CD8+ cytotoxic T lymphocyte.

Front 13

What is a superantigen?

Back 13

A protein in its native form that has the ability to bind to the outside of certain class II molecules; the result is that a very high percentage of TCD4+ cells (20%) respond.

Examples: Toxic shock syndrome, Kawasaki syndrome, and food poisoning

Front 14

Describe MHC class Ib presentation

Back 14

Activates CD8+ T regulatory cells and NK cells.

Binds peptides derived from bacterially-derived and self heat shock proteins (involved in protein folding); thought to indicate cell stress.

Front 15

Describe CD1 presentation

Back 15

Expressed on a restricted set of cells (Langerhans, dendritic, and B cells).

The presented material is not peptide, but rather a cell wall component made up of mycolic acid and lipoarabinomannan; appears to play a major role in responses to certain pathogens such as the Mycobacteria