Lecture # 12 MHC Restriction Recap Antigen Processing and Presentation - Class I Flashcards
MHC and applications to transplantation
Slight differences in MHC from donor to acceptor causes allergy.
Super antigens
Bind to the outside of the MHC/TCR VB3 NOT VIA MHC1; Polyclonal activation of VB3+ T Cells; cytokine storm (cause toxic shock syndrome) and deletion of T Cells; recognize by T cells without being processed into peptide;
JITT #5 Q# 1; From the class I deficiency study, Tatiana and Alexander had normal delayed type hypersensitivity response to tuberculin and candida (fungal organism) Why do you think this is?
1) Candida and Tuberculin are fungal and bacterial respectively, both are extracellular pathogens
2) We know that MHC I is deficient, MHC II must be at work
3) MHC II specifically works against extracellular pathogens
MHC I combats which type of pathogen?
Viral
MHC II combats which type of pathogen?
extracellular
Why is deficiency such a big deal when we are considering CD8+ and CD4+?
Because if we are deficient in an MHC, then there is no CD8+ or CD4+ development!!! Low levels of T Cells!!
What type of peptides do CD4 T cells recognize?
CD4+ cells recognize bacterial peptides in the context of MHC II
Antigen processing
refers to the generation of peptides from an intact antigen that involves modification of naive protein
Antigen presentation
refers to the display of the peptide at the cell surface by MHC molecules to T cells
In what region do peptides recognized by CD8+ T Cells originate from?
Pathogen peptides are from the cytosolic compartment
In what region do peptides recognized by CD4+ T Cells originate from?
Pathogen peptides are from the endosomal/vesicular compartment
Cross Presentation pathway (Class I )
Exogenous antigens from a dying virus infected cell that is phagocytosed by a DC can be transported to the cytosol
Class II pathway
BCR mediated endocytosis, peptides are presented; MHC II expression and CD4+ effectors
What types of peptides can APC express?
Professional APCs present pathogens to both CD4+ and CD8+
Which type of MHC presentation is TAP specific for?
MHC class I presentation
How do peptides from the cytosol get into the ER to be loaded to MHC Class I molecules?
By TAP
Proteosome
large protease complex that degrades cytosolic proteins
What are the two types of proteosomes?
Constitutive proteosome and immunoporteosome
Constitutive proteosome
alpha and beta subunits induced to become the immunoproteosome by interferon gamma
Immunoproteosome
LMP2, MECL-1, LMP7 subunits
PA28
compound that binds to ends of inducible proteosome, opens up the ends and increases the rate at which peptides are releases. induced by interferon gamma
ERAP
chops peptides more to produce a peptide that better fits to MHC go to slide 22right now
Viral Evasins
degrade class I or bind to TAP and inhibit peptide loading
