I am trying to work out exactly how PHA-L induces proliferation of T cells. I have search the literature and have so far just found explanations of indirect CD3 cross-linking (but no direct evidence), and a requirement of monocytes/ IL-2.
I am particularly interested in what ligands PHA is binding on T cell surfaces, and whether there are any reports of PHA binding lectins expressed on T cells.
It would be great if anybody has more information on this topic, and/or if someone could suggest any relevant literature for me to read.
Many thanks!
Hi Katy,
PHA-L is itself a lectin, one of the many legume lectins. This particular one causes severe allergy by switching on a runaway meitogenic event. It binds to the sugars on the proteins presented on the surface of cells, one of the inner residues near the surface, possibly even the fucose residue where there is such a branch. Immune system proteins are a subset of these glycosylated protein on cell surfaces, that PHA-L binds. What that binding does is unknown to me. The runaway meitogenesis causes the unfortunate cells to rupture and the swamping of the system with histamine, hence the severe allergy. Be sure not to eat uncooked beans! Although broad beans do not trigger such an effect. Weird.
Pierre
The specific sites of PHA:T-cell interaction still seem to be poorly defined although some literature suggests that PHA initiates activating signals via the CD2 receptor (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1453876/, http://www.ncbi.nlm.nih.gov/pubmed/2484882). In lectin-based T-cell activation, downstream mechanistic differences have been observed compared to antigen-specific activation as lectins cause Ca2+ influx via different calcium channels than those utilized by CD3-specific signaling pathways (http://www.ncbi.nlm.nih.gov/pubmed/22020731).
Lectins exert their action on immune cells by cross linking multiple cell surface glycoproteins and not just one, there by initiating the activation to proliferation etc. PHA may also work in the similar fashion. If you are looking for a PHA ligand....... most probably you will end up with multiple proteins with other reported functions. However, It would very interesting if you can find a specific PHA ligand.
Hi,
although it is not a current topic as I see, there is some information available concerning the substrates of L-PHA on T cells: L-PHA is a tetravalent plant lectin and is a commonly used T cell mitogen that binds specifically to Mgat5-modified glycans. Mgat5-/- T cells were completely unresponsive to L-PHA (PMID: 1121786)
Hi Minnie,
I found this article: https://www.nature.com/articles/3301807
It seems to me that they use L-PHA stimulated T cells for clinical applications but you need to check it to be sure.
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