Maloney Lab meeting, 20140917

Maloney lab meeting

Glycolipids between VT500 and Daudi cell lines

  GC
  LC
  Gb3 (aka CD77), a rare CD## is actually glycolipid
  Gb4


Lipid raft in cell membrane contain high concentration of glycolipids

Lipid raft research bridges glycolipid and signal transduction

Gb3/CD77 = globotraisocyla ceramide =  glycosphinglolipid
   Defines pk blood group antigen
  Receptor for Shiga toxin/verotoxins
 Burkitt's lympphoma associated antigen
 CD77 is a marker for germinal center B cells


Shiga toxin targets Gb3, arguing that some Gb3 should also bind some normal human proteins.

Shigtoxin is also called Verotoxin in Canada.


Gb3 may be invovled in cell-cell interaction

Bacterial cells can shutdown germinal cells and eliminate immune response memory by targeting Gb3.

Gb3 is involved in apoptosis signaling

Shiga toxin binding of Gb3 induces apoptosis, and this can be triggered with B-subunit alone.

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Burkitt's Lymphoma is a maligant lymphomas of African children.
Associated with malaria zones and EbV-infection

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Germinal center cells
  Antigen recognition by surface antibody (CD19 part of co-receptor complex).
  Antigen presentation to CD4+T helper cells
  Affinity maturation of antibody responses/Somatic hypermutations
  Isotype switching

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Role of CD77 in Germinal center B cells
  CD19 in one cell binds Gb3 on another cells. CD19 is a glyco-protein with a large extra-cellular protein domain.
  CD19/CD77 binding as adhesion mechanism
  MHC classII expression


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Interferon-alpha receptor subunit 1 contains a Shiga toxin like amino acid sequence.
CD19 also has a Shiga toxin like amino acid sequence. This sequence is distributed in 3 regions, with quite some distance between them.


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VT500
Daudi

How are they different in Gb3?

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apoptosis inducers: capersysin(?),
JC-1 dye to monitor mitochondrial membrane polarization

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Search of Shiga-toxin like sequence pattern can be improved by HMM.


Shiga-toxin is also shared by Shegalla boydii 


Todo: orthologs of CD19 in other mamals, and their shiga toxin motifs. 
It turns out that Shiga toxin does affect germ-line B cells in mouse, so mouse CD19 is not expected to has shiga-toxin binding motif. Well, how about Neanderthal?