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Immuno Lec 2
Question | Answer |
---|---|
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. |