The Magic of Antigen Presentation Flashcards
Class I MHC molecules are encoded by these three genes in humans on this chromosome
HLA-A, HLA-B, HLA-C; on chromosome 6
- one set from mom and one from dad = 6 genes
The 1500 variations among individual humans in the MHC I heavy chains
polymorphism
= many peptides can bind in the groove and because the focus of binding is on the ends of the binding groove, binding in the center of the peptide can be promiscuous
T or F. Although polymorphism exists in the Class I MHC heavy chains, the beta-2 microglobulin is identical in everyone
T!
Open at both ends, holds a peptide of 13-25 AAs in length
Class II MHC
one gene in humans, on this chromosome makes this to generate Class II MHC
chromosome 6; HLA-D
- ~7000 variations among individuals, resulting in polymorphism
- anchored along the grooves
endogenous peptides
MHC class I
- could be proteins made inside that cell
- or peptides made by a virus or other microorganism replicating inside that cell
There are the main immune cells that “checks out” the advertising on the MHC I billboard
CTLs
they will destroy cells that display foreign (eg. viral peptide)
- ‘billboards’ are constantly being replaced with new ones, so the cell’s status is continually being updated
Antigen processing and presentation by class I MHC
- defective or damaged proteins in the cell are chopped up into peptides by proteasome
- some peptides transported by TAP1 and TAP2 to ER
- peptides that fit are loaded into MHC I
- moved to Golgi
- then to surface of the cell
antigen presentation by class I MHC : APCs
- IFN-gamma produced during innate immune response (eg. by NK cells stimulate by LPS) causes up-regulation of specialized proteins in APCs
- these proteins replace the standard proteins in the proteasome to create peptides with hydrophobic ends that are favoured by TAP proteins and MHC I
- so MHC I peptide presentation is ENHANCED n APCs compared to other regular cells
exogenous peptides
- typically foreign
- cells that acquire them are special cells of the immune system called professional APCs (sample proteins in the environment outside regular cells)
- MHC II
- Th cells
antigen processing and presentation by class II MHC
- in ER of an APC, MHC II is bound to an invariant chain peptide that protect it from picking up endogenous peptides
- invariant chain guides the MHC II to Golgi and endosomes
- protein from outside are digested in phagosome
- phagosome with exogenous peptides fuse with endosomes containing MHC II
- invariant chain, now CLIP, is replaced with peptide
- and are transported to the cell surface where they are displayed to Th cells
co-stimulatory molecule on the APC binds its receptor on the Th cell
B7 with CD28 = second signal!
considered the most important of all APCs because they can activate virgin T cells
dendritic cells
- sentinel cells in skin and throughout the body that can be activated by two signals: TNF or PAMPs
Dendritic cells can be activated by these two signals
- TNF produced by immune cells or by other chemicals released from dying cells (destruction by microbes)
- PAMPs which are recognized by the toll-like receptors ON or INSIDE DCs
activating dendritic cells and their antigen presentation process
- phagocytose prey, travel from site of infection through lymphatics into a lymph node (~day); loads peptides into MHCII and increases expression of MHC I
- reaches a lymph node, MHCI and MHC II are loaded onto surface, along B7 molecules and communicate their peptide info to cognate TCRs on virgin T cells
- with B7 as second signal, activates T cell
