Immunology - HLA and MHC1 Pathways

*HLA = Human Leukocyte Antigens

  • include MHC 1/2 classes
  • other specific HLAs for certain diseases

*MHC = Major Histocompatability Complex

  • MHC 1 vs. MHC 2
  • MHC 1 = "call Toll free 1-800, but beta micro charge after"
    --> MHC1 = TCRs and CD 8 / beta2-microglobulin
  • MHC 2 = "show 24 is INVARIANT"
    --> MHC2 = TCRs and CD 4 / 4 for helping / invariant chain

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MHC Class 1

  • on surface of all human cells
  • recognized by cytotoxic T cells (CD8)
  • MHC 1 = "call Toll free 1-800, but beta micro charge after"
    --> MHC1 = TCRs and CD 8 / beta2-microglobulin

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*MHC 2 = Major Histocompatability Complex 2

  • MHC 2 = "show 24 is INVARIANT"
    --> MHC2 = TCRs and CD 4 / 4 for helping / invariant chain

Clinical Cases

Clinical Case

Notes:

  • note that

Clinical Case

MHC Class 2

  • on surface of ONLY APCs
  • recognized by Helper T cells (CD4)

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Clinical Case

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Notes:

  • MHC 1 vs 2
    --> the MHC2 class, since it presents exogenous foreign antigens, it endocytoses them into endosomes
    --> these endosome are first fused with lysosomes
    --> become endolysosomes
  • endolysosomes are acidic (only for MHC 2 and exogenous foreign)
    --> the acidification of endolysosomes is needed for MHC 2 since it's invariant (plunger) is removed by the acidicfication
    --> that blocks the antigen binding spot until the MHC 2 transport vesicle fuses with the endolysosome

HLA MHC 2 Case #2

Notes:

  • note that the invariant chain of the MHC 2 class AP protein is degraded in endolysosomes
  • the invariant chain is a blocker at the end of the MHC 2 during its transport to the endolysosome
    --> to make sure no antigens or proteins attach to its binding site
  • once in the endolysosome, acidification causes the invariant chain to break down in order to make room for ingested foreign antigens to bind to the MHC 2 to be presented to CD4 = helper T cells
  • think that MHC 2 want to stay INVARIANT before they reach the forein antigens

Clinical Case

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*Main HLA Antigen Diseases

  • H3= "H3 = last HUMMER "
    --> hemochromatosis = H3 HLA
  • HLA B27 = "PAIR of B27 bombers"
  • DQ2/DQ8 = "I 8ate 2 much GLUTEN at Dairy Queen = DQ"
  • DR4 = "a RHEUM = room has 4 walls"
    --> Rheumatoid Arthritis

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*Ubiquitin Protein Catabolism

  • process that tags proteins for degradation so they can be attached to MHC 1/2 for APCs
  • ubiquitin ligase is the enzyme that tags the proteins for degradation by a proteosome complex

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