Antigen Presentation Flashcards
CD8 on T cell interacts with ___ domain on MHC I
alpha 3
what binds to MHC I?
TCR of Tc cells and CD8
T or F. Peptides will bind to closed groove of MHC I
T (8-11 AAs)
anything longer = will not fit
shorter = will but won’t stay very long
for MHC Iwhere in the cell are peptides loaded?
endoplasmic reticulum
where do peptides come from to be loaded to MHC I?
comes from inside cell (endogenous peptides)
where is MHC I located
on all nucleated cells
CD4 on T cell interacts with __ and __ domains of MHC II
Beta 2 and alpha 2
what are MHC I made of?
heavy chain + B2-microglobulin
what are MHC II made of?
alpha and B chains
what binds to MHC II
TCR of Th cells and CD4 (helps with anchoring and recognition)
where do peptides bind to MHC II?
open ended groove
12-22 AAs
where in the cell are peptides loaded on MHC II?
endosomal pathway
where do peptides comes from for MHC II?
outside/exogenous peptides
which types of cells express MHC II?
professional APCs and cytokine-activated cells
ex: endothelial cells normally are not APCs but when activated by cytokines could become APCs
TAP
transporter associated with antigen processing
peptide transport to the rough endoplasmic reticulum
ATP-dependent
2 subunits = TAP1 and TAP2
transports 8-16 peptides
Tapasin
tells MHC to move towards TAP = where peptides come in
ERAP
breaks down peptides to ensure it is 8-11 AAs long
if correct size = dislodges ERp57
the types of antigens that uses exogenous pathway
peptides from internalized bacteria or viruses
internalized self proteins
cells that present antigens for exogenous pathway
antigen presenting cells
cells that recognize Ag+ MHC II for exogenous pathway:
CD4 + Th cells
criteria for APCs
must express MHC II
must be able to deliver a co-stimulatory signal
professional APC
dendritic cells = most effective; do majority of naive T cell activation
macrophage = must be activated by phagocytosis
B cells = must be activated by antigen
non-professional APC
any cells inducible by interferon (IFNy)
= skin fibroblasts, glial cells, pancreatic beta cells, vascular endothelial cells
MHC II peptide loading
alpha and beta chains made in RER
invariant chain immediately binds to MHC II in RER
- helps with MHC II folding - chaperone
- prevents peptides in RER from binding to MHC II
- directs MHC II out of RER to early endosomes
three MHC II complexes combine with 3 invariant chains to form a nonamer
bare lymphocyte syndrome type I
- lack surface MHC I
- mutated Tap 1 or 2 = can’t move peptides into RER if can’t load MHC = unstable = will not go to surface
- Tc decreased, normal Th
- do well with viral but not with bacterial infections
- necrotizing skin lesions, respiratoru nacterial infections
- excessive NK cell activation, thymic selection
bare lymphocyte syndrome type 2
- lack surface MHC II
- usually due to transcription factor defects
- massive decrease in Th cell activation, normal Tc
- severe combined immunodeficiency
- no help for B cells
three characteristics of MHC
- polygenic (multiple genes)
- polymorphic (multiple alleles for each gene)
- co-dominant (paternal and maternal genes are co-expressed)
mouse MHC genes
histocompatibility-2 (H2 genes)
human MHC genes
human leukocyte antigen (HLA) genes
types of antigens used in an endogenous pathway
peptides from replicating viruses
intracellular misfolded self-peptides
target cells for endogenous pathway or cells that present these antigens
any nucleated cell expressed MHC I
cells that recognize Ag + MHC I
cytotoxic T cells (CTLs = Tc = CD8+ cells)
describe the cytosolic processing of antigens
- protein infects cell
- protein ubiquitination
- proteasome breaks down proteins into peptides and eventually AAs
- this is loaded onto MHC I
where are immunoproteasomes found?
in all professional APCs and also in the presence of IFNy/TNFa during an infection
define immunoproteasomes
special proteases that increase speed and frequency of 8-10 AA peptide formation = binds MHC I
describe MHC II peptide loading
MHC II and invariant chain binds
invariant chain is digested and remnant (CLIP) stays with MHC II
HLA-DM catalyzes CLIP exchange with peptide
HLA-DO binds to HLA-DM and negatively regulates activity
these are non-classical MHC II
HLA-DM and HLA-DO
four mechanisms for uptake of foreign lipids by cells
- apolipoprotein E-lipid complexes bound to LDLR
- phagocytosis of pathogens
- C-type lectins bind mannose residues on glycolipids
- scavenger receptors - bind modified LDL and apoptotic cells
lipid loading and exchange
any one of the four mechanisms
then… exchange of lipids through actions of accessory molecules:
CD1e
Saposins - binds lipids, extracts from membranes and transfers to CD1 identified in several lipid storage disorders
T or F. Pathogens interfere with antigen presentation pathways
T
