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Immuno Lec 2

Four major histocompatability complex molecules MHC1, MHC2, TCR, Ab
TCR vs Ab TCR - Processed Ag. Ab - Native Ag.
TCR and antigen TCR is for intracellular pathogens. recognize through cell-cell contact. Antigens are associated with MHC.
MHCI Alpha chain with 3 domainds. B2-microglobulin. CD8+ T cells. Noncovalent. Located on All Nucleated Cells. A3 is integral. a1+A2 = Ag binding groove.
MHC2 a1,a2,b1,b2. A1,b1 = antigen binding. a2,b2 = integral. CD4+ T cells.
Where are MHC1 and MHC2 cells located? MHC1 - All Nucleated Cells MHC2 - APC. Macro/mono, b lymphocytes, dendritic cells, Microglia, thymic stromal cells
HLA complex portion of human genome that contains the MHC genes. Polymorphic. multiple alleles at each locus. 6 to be exact.
MHC Polygenic. Class 1 and Class 2 encode similar but not identical proteins
Class I Loci A, B, C. Express up to 6 different MHCI proteins
Class II Loci DP, DQ, DR Express up to 12 Different MHCII Proteins.
MHC inheritance Co-dominant. Maternal and paternal alleles expressed.
Two types of antigens endogenous and exogenous
endogenous antigen cytosolic. 8-10aa. host normal, host abnormal. intracellular pathogen.
exogenous antigen endocytic. microbe. toxin. 13-20aa.
MHC1 antigen processing host and viral proteins synthesized in cytosol. Mark with ubiquitin. proteosome processes to optimal size. transport via TAP to ER. Calnexin holds the MHCI in the ER. Attachs B2. Peptide/MHC1 go to golgi, then cell surface.
MHC2 antigen Processing Brought into cell via endocytosis. then pH of endosome denatures protein, degraded by proteases. MHCII held in ER by Invariant Chain Li and calnexin, targetted to endosome.
APCs express which MHC BOTH.
T Cell Receptor MHC Restricted. Cannot recognize Ag without MHC. All TCR on a given cell are identical.
TCR Structure. Monovalent. Va, Vb, Ca, Cb. intrachain and interchain disfulide bonds. A = light. B = heavy. Carbohydrate attachment.
TCR Antigen Binding Site Combination of CDR (complimentarity determining region) from the alpha and beta chains. the V region of the a and b chain.
How does CD4 recognize antigen? Antigen/MHCII Complex on APC. noncovalent.
How does CD8 recognize antigen Antigen/MHCI complex on target cell.
TCR Complex TCR is alphabeta. CD3 complex are 3 TM Protein dimers, associate with TCR, for signal transduction.
TCR Gene Rearrangement 1) Pre-TCR = B Chain + surrogate a chain 2) coreceptor expression, CD4+, CD8+ 3) Gene Rearrangement, add a chain
Positive Selection Occurs in cortex. Thymic cortical epithelial cells express MHC1, MHCII. They mediate positive selection.
What mediates positive Selection Thymic Cortical Epithelial Cells
Negative Selection At Cortico-Medullary boundary Mediated by IDC/macrophages Strong interaction with self/MHC results in death Establishes central tolerance.
What mediates negative selection IDC and Macrophages
Peripheral Tolerance Tolerance to self antigens not encountered in 1* lymphoid organs. Occurs during T cell activation.
Created by: nady