Antigen Processing & Presentation

MHC antigens codominate 53

Mixed Lymphocyte Reaction 38

Self MHC Restriction of T Cells CD4+ & CD8+ cells Antigen must be in cleft of MHC MHC polymorphism ~500 antigens/cleft Self MHC Restriction of T Cells

Haplotype Restricted Cytotoxicity 56

“Antigen Pulse” “Antigen pulsed” macrophages T helper (CD4+) cells can only be stimulated by macrophages with the same MHC Class II Cytotoxic (CD8+) T cells can only be stimulated by macrophages with the same MHC Class I “Antigen Pulse”

T Cell Activation

MHC I: Biological function 44

MHC II: Biological function 47

MHCII: Biologogical function (2) 46

MHCII: Function 50

Role of Antigen Presenting Cells Immunize with native protein Boost with native protein B cell & T cell response Boost with denatured antigen T cell response only 2 different mechanisms APC for cell mediated & humoral Role of Antigen Presenting Cells

Antigen Presenting Cells Professional APC Dendritic cells Macrophages B Cells Non Professional APC Fibroblasts Glial cells Thymic epithelial cells Vascular endothelial cells

Lot MHC-II co-stimulate activate T helpers Dendritic cells

Macrophages Engulf microbe first co express with B7 membrane protein digest antigen bind to MHC-II co express with B7 membrane protein Macrophages

Constitutively express MHC-II activated then express B7 B Cells

Two Presentation Pathways Cytosolic- MHC-I endogenous antigens Endocytic - MHC-II exogenous antigens Two Presentation Pathways

Cytosolic Pathway: Endogenous Antigens Ubiquitin & ATP Bind to peptide proteasomes Bind ubiquitin peptide transport Assembly of peptides in MHC-I Rough Endoplasmic reticulum Export to membrane Cytosolic Pathway: Endogenous Antigens

TAP proteins Transports associated with Antigen Processing TAP-1 TAP-2 Transfer Peptides from proteosome to RER TAP proteins

TAP-1 TAP-2

Calnexin & MHC-1

Assembly in RER TAP-1 TAP-2 transport into ER Bind to Calnexin MHC-I Add peptide to MHC-I Release calnexin Transport to Gogli Assembly in RER

Endogenous Pathway MHC-i

Endocytic Pathway: Exogenous Antigens endocytic vesicles peptide transport Assembly of peptides in MHC-II Endocytic Pathway: Exogenous Antigens

Endocytic Route From Outside- phagocytosis From Inside Fuse Make MHC-II Bind Invariant chain CLIP- digests invariant chain Fuse MHC-II & clipped I & peptide peptide displaces clipped I chain Endocytic Route

Invariant chain & MHC-II

Exogenous Pathway MHC-II

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