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MHC_Bergeron

QuestionAnswer
purpose of MHC bind peptides for display to appropriate lymphocytes, aka antigen presentation
MHCI CD8, endogenous, all nucleated cells
MHCII CD4, exogenous, displayed on APCs but can eb induced in presence of cytokines, activation of effector functions in T cells...like naive CD4s become Th1,Th2, etc.. also activation of B cells.
APCs monocyte derived phagocytes like macrophages, dendritic cells, B cells.
cross presentation when exogenous Ag leaks into the cytosol from endosomes.
structure of MHCI alpha1,2,3 and beta2 microglobulin. peptide binding cleft/groove is alpha 1 and 2. bind short peptides(8-12aa). MHCI present Ag to CD8's TCR.
structure of MHCII alpha1,2 and beta1,2. peptide binding cleft/groove is alpha1 and beta1. longer peptides(13aa). MHCII present Ag to CD4's TCR.
chromosomes for MHC genes Chr6: aplha chain of MHCI and alpha beta chains of MHCII. TAP1 and TAP2 Chr5: invariant chain, beta2 microglobulin
HLA genes HLA-A,B,C for MHCI HLA-DP,DQ,DR for MHCII (many have extra DR) HLA genes are polygenic and highly polymorphic. MHC inherited from both parents but co-dominantly expressed on cell surfaces.
Ag presentation all nucleated cells can display MHCI when there is a intracellular parasite. MHCII expressed on MO, DC, B-cells and activated T-cells...but can be induced by cytokines.
regulation of Ag presentation upregulation: proinflammatory cytokines, INF stimulation. downregulation: TGF-b, IL-1, IL-4, IFN-a
MHC-I Ag presentation pathway TAP1 and TAP2 ER membrane transporters that bring in peptides from cytosol. chaperones for MHCI - calnexin and thioredoxin until beta chain binds. tapasin/ERp57/calreticulin complex until peptide binds. loaded MHCI transported to cell surface via golg
MHC-II Ag presentation pathway peptides produced in acidified andocytic vesicles like endosomes and phagolysosomes. MHCII in ER bound to invariant(Ii) chain. peptide loading in edosomal compartments.
Cathepsin Ii cleaved by cathepsin leaving a "clip". clip heterodimers take off clip when peptide needs to bind.
proteasome/immunoproteasome ATP multisubunit protease complex in cytosol. degreadation of ubiquitinated proteins into peptides of 8-12 residues. 4 rings of 7 subunits.abba strucure INF-g stimulation -> immunoproteasomes and proteasome activator(PA) synthesis induced
Ubiquitin ubiquitin activating enzyme E1 -> U transfered to U carrier protein E2 -> U transfered to protein with U protein ligase E3 -> polyUb chain made that is the "tag" for proteasome
co stimulation for MHCII CD80/CD86(B7) interaction with CD28
superantigen cross link MHCII and TCR. activate CD4 witout any co-stimulation and independently of peptide binding groove. create a cytokine storm and depletion of activated T cells. eg: toxic shock syn, staphylococcal enterotoxins
Created by: kokila