8. Antigen presentation to T lymphocytes Flashcards
why don’t B cells need antigen presentation
they secrete antibodies that look for pathogens
where does antigen presentation to T cells take place in the body?
secondary (peripheral) lymph organs
T cells recognize and respond to… NOT…
cell-associated antigens
soluble, cell-free antigens (role of B cells)
properties of antigens recognized by T cells
most T cells recognize only short peptides
peptides they recognize depends on MHC restriction
what is antigen processing
the generation of peptides from native proteins
intracellular pathogens from the cytosol
transported to the ER and loaded onto MHC I
include viruses and certain bacteria
found in both somatic and immune cells
presented directly
intracellular pathogens from vesicular compartments
involved in endocytosis and secretion
loaded onto MHC II so helper T cells can alert B cells
characteristics of cytosolic pathogens
degraded in cytosol
bind to MHC I
presented to CD8 T cells
causes cell death of APC
found in somatic and immue cells
characteristics of intravesicular pathogens
degraded in endocytic vesicles
bind to MHC II
presented to CD4 T cells
causes macrophage activation to kill intravesicular pathogen
restricted to immune cells
characteristics of extracellular pathogens
degraded in endocytic vesicles of B cells
bind to MHC II
presented to CD4 T cells
causes activation of B cells to secrete Ig and eliminate extracellular pathogens
what is cross-presentation of antigens
the ability of APCs to take up, process and present antigens from an outside source with MHC I to CD8 T cells
this cell itself is not infected
important in immunity against tumors
what is cross-priming
the activation of naive CD8 T cells into activated cells by cross-presentation
what is the autophagy pathway of pathogens
the delivery of cytosolic antigens for presentation by MHC II
deals with self antigens
how are proteins degraded in the cytosol
carried out by the proteasome that has a 20S catalytic core and 2 19S regulatory caps
protein is ubiquitinated in the cytosol
ubiquitin chain is linked to K48 and recognized by the 19S cap, unfolded and chopped up into short peptides that can be presented on MHC
what are TAP1 and TAP2
proteins that transport peptides in the cytosol to the ER before binding MHC I
what is ERAP1
ER aminopeptidase associated with antigen processing in the cytosol
trims the amino terminus if it is too ling to bind MHC
its expression is increased by IFN-y stimulation
mechanism of peptide processing and loading on MHC I molecules
partially folded MHC I alpha-chain binds calnexin
B2 microglobulin binds and calnexin is released
complex binds to calreticulin, ERp57 and TAP
cytosolic peptides created by protease are delivered to the ER by TAP
the peptide binds the MHC I molecule to complete its folding
MHC I is released from the TAP complex and exported to cell membrane
which proteins make up the peptide loading complex for MHC I
calreticulin, tapsin, ERp57, TAP
how are peptides that bind to MHC II generated
antigen is taken up from extracellular space via endocytosis
acidification of vesicles activates proteases to degrade antigen into peptide fragments
vesicles containing peptides fuse with vesicles that contain MHC II
what is the invariant chain
a molecule that directs newly synthesized MHC II molecules to acidified intracellular vesicles
how does the invariant chain bind MHC II
invariant chain (li) binds in the groove of MHC II
li is cleaved to leave a fragment bound to MHC II and to the membrane
further cleavage leaves a short peptide fragment (CLIP) bound to the MHC II molecule
what facilitates the loading of antigenic peptides onto MHC II molecules
HLA-DM
mechanism of peptide processing and loading on MHC II molecules
MHC II binds the invariant chain in the ER
invariant chain is cleaved leaving CLIP bound to the MHC II
the phagolysosome with the antigen peptide fuses with the MHC II vesicle
HLA-DM binds to MHC II, releasing CLIP
MHC II travels to cells surface
what is different about how MHC I and II acquire the peptides they bind
- MHC I acquire peptides from cytosolic protein degradation via proteasome with TAP assisting peptide transport
- MHC II bind invariant chain which inserts CLIP. followed by cleavage in acidic endosomes
diverse rolls of MHC II
activating macrophages
aiding B cell antibody production
regulating immune responses
3 ways the diversity of antigen presentation by MHC attained
polygenic: several MHC I and II genes
polymorphism: many variants
codominance: expressed from both inherited alleles
what does MHC polymorphism ensure
the population will not succumb to a new pathogen or a mutated one because at least some individuals can develop an adequate immune response to it
MHC diversity is limited to…
the binding site - T-cell recognition of antigens is MHC restricted
3 properties are affected by MHC polymorphism;
- the range of peptide bound
- the conformation of the bound peptide
- the direct interaction of the MHC molecule with the TCR
what is an exception to MHC presentation to T cells
non-peptide antigen presentation
how are non-peptide antigens presented to T cells
non-classical class I molecules
CD1 family of proteins
MR1: MHC class I related protein
