53-MHC and Antigen Presentation Flashcards
T cells
effector cells of adaptive immune response, 3 types
CD8 t cell
t killer cells
recognize infected cells and kill them
CD4 t cell
t helper cells
regulate function of other cells and release cytokines
gamma delta t cell
like innate cells, mucosal immunity
activation of T cell
requires 3 signals
activation
survival
differentiation
signal 1 for t cell
activation
from TCR
activation of TCR by antigen/MHC
signal 2 for t cell
survival
from costimulatory receptors of antigen presenting cells
CD28 binding to B7.1 and B7.2
signal 3 for t cell
differentiation
from cytokines produced by antigen presenting cells
antigens
proteins or large polysaccarides that are recognized by T cells using TCR
epitopes
small portion of antigens recognized by TCR
TCR/MHC interactions
required for T cell activation, need 10-20 interactions, naïve cells need more
where are MHC class 1 found
nucleated cells
NOT RBC or platelets
MHC class 1 activate what
CD8 t killer to eliminate pathogens
where are MHC class 2
antigen presenting cells
macrophages
B cells
dendritic cells
MHC class 2 activate what
CD4 t helper to control adaptive immune response
MHC class 1 peptides
intracellular (mostly cytosolic proteins, some ER)
dendritic make extracellular
MHC class 2 peptides
extracellular
dendritic make intracellular
MHC class 1 structure
2 subunits
alpha-binding
beta 2 microglobulin-stabilize
bind short amino acids 8-10
anchor residues
amino acids on end that bind to MHC
loading MHC class 1
- chaperone calnexin facilitates forming MHC/b2microglobulin
- transfer to chaperone calreticulin/ERp57/tapasin that interacts with TAP
- peptides produced in cytoplasm and transferred to ER with TAP complex
- peptides cleaved to 8-10 using ERAAP protease and loaded onto MHC class 1
- released after high affinity peptide is loaded
viruses inhibiting MHC class 1
encode for protein to inhibit MHC class 1 evade CD8 T killer
combat viral suppression of MHC class 1
NK cells recognize cells with low MHC class 1 and kill them (presence of receptors on NK that recognize MHC class 1 and suppress NK function)
loading MHC class 2
extracellular- pathogens loaded by phagocytosis, non specific antigens loaded by macropinocytosis
intracellular-loaded by autophagy
MHC class 2 structure
2 proteins: alpha and beta which make peptide binding cleft
bind loner peptides, 12-20 amino acids
MHC class 2 binding peptides
MHC class 2 made in ER and binds invariant chain then transported to endosome Activation of antigen presenting cell acidifies endosome degrading invariant chain and proteins peptides loaded onto MHC class 2 by HLA-DM
pathogen superantigens
bind TCR and MHC
from bacteria, virus, mycoplasmas
cause atypical activation of t cells and cytokines
create systemic toxicity and immune suppression needed for microbial pathogenicity
Septic Shock
CD4 T cell activation
different function depending on antigen presenting cell
dendritic-activate naive t cell
macrophage-cell mediated immunity
b cell-humoral immunity
Dendritic cell activating CD4
activate naive T cell for clonal expansion and differentiation into effector T cell
Macrophage activating Cd4
macrophage activation, activation of effector CD4 T cells at infection and inflammation
cell mediated immunity
B cell activating CD4
b cell activation and antibody production, humoral immunity
cross presentation
dendritic cells present extracellular on class 1 and intracellular on class 2 critical for activation of naive CD8 T cells
DC licensing
activation of dendritic cells by CD4 T cells
MHC locus
contains 200 genes
most gene rich regions in genome
on chromosome 6
involved in antigen presentation and peptide loading
MHC class 1 genes
HLA A, B, C
MHC class 2 genes
DR, DQ, DP
polymorphism
multiple alleles for same gene
MHC are most polymorphic genes in humans
Class 1 higher number of alleles than Class 2
polygeny
having multiple genes with same function
function of polymorphism and polygeny
increase potential number of peptides that can be bound by MHC
MHC haplotype
combination of MHC genes on single chromosome
inherited as a single gene
new MHC alleles and haplotype arise from point mutations
Major diversity in MHC is where
peptide binding groove/cleft
function of diversity in MHC peptide binding groove
each allele can bind peptide with different anchor residue
increase total pool of peptides that can be bound
autoimmune disorders
linked to specific haplotypes of MHC Class 2
presence of pathogenic haplotype
does not cause disease but increases disease susceptibility
why does pathogenic haplotype increase disease susceptibility
better able to bind self antigens, induce cytokine production, promote polymorphisms that increase MHC or protein expression
