Signaling Meeting Minutes December 2009

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2nd December - Documentation of T cell signaling structure

These images show the structure that we have set up to capture T cell signaling.

Initiation

Initiation.jpg

Transmission

Cascade.jpg

Phos.jpg

Transmission.jpg

Consequence

Consequence.jpg

Termination

Termination.jpg


Comments from Alex

December 7, 2009

Sandra and Jen,

Thanks for your work on these graphs. In general I like the approach, but I have a couple of comments:

1. T cell receptors bind the unique combination of MHC molecules and the peptide antigens held by them. Residues on both the MHC molecules and peptides are contacted. This is extremely well worked out and documented in the literature. In some cases, the peptide itself is not even required, and in other cases a lipid antigen or polysaccharide is present instead of a peptide antigen.

Furthermore, in the GO we define "MHC protein complex ; GO:0042611" as follows:

A transmembrane protein complex composed of an MHC alpha chain and, in most cases, either an MHC class II beta chain or an invariant beta2-microglobin chain, and with or without a bound peptide, lipid, or polysaccharide antigen.

We have similar definitions for the more specific terms "MHC class I protein complex," "MHC class Ib protein complex," and "MHC class II protein complex".

Thus, the term, "initiation of T cell receptor signaling by binding of a peptide antigen to the T cell receptor" is formulated incorrectly. The correct term name would be "initiation of T cell receptor signaling by T cell receptor binding of a MHC protein complex."

Moreover, there should be no direct relationship between "peptide antigen binding" and "initiation of T cell receptor signaling by T cell receptor binding of a MHC protein complex." The TCR receptor never binds peptide antigen by itself, but always in combination with an MHC protein complex, which by definition may or may not contain a peptide antigen.


2. Regulation of gene expression is an important consequence of TCR signaling. However, there are other, more immediate consequences in many cases. One additional term needed here is "regulation of T cell mediated cytotoxicity as a consequence of T cell signal transmission". This term is also an is_a to "regulation of T cell mediated cytotoxicity ; GO:0001914". An argument could be made that this is always positive regulation, but I'm not quite sure since antagonist peptide may block cytotoxicity. Probably we should include both positive and negative regulation terms.

Another term needed is "establishment of T cell polarity as a consequence of T cell signal transmission." This term is also an is_a to "establishment of T cell polarity ; GO:0001768".

In fact, for these terms, I would prefer the phrase "...as a consequence of T cell receptor signal transmission" instead, since we are concerned with signal transduction events cause by the T cell receptor, and not some of the other pathways in the T cell.

8th December

Receptor recycling

Moved "receptor recycling" to be under "signaling process". A number of recycling terms are missing and Sandra will write these out on paper during the week and pass them to Jennifer to be entered before the next meeting.

Action: Sandra: Write out recycling terms.
Action: Jennifer: Enter recycling terms.

Termination of T cell signal transduction

Additional parentage given to "termination of T cell signal transduction":

[i]negative regulation of T cell receptor signaling pathway
---[i]termination of T cell signal transduction
[i]termination of signal transduction
---[i]termination of T cell signal transduction

Signal initiation and the MHC Complex

Improved the relationships connecting initiation of T cell signaling to the binding terms in the function ontology:

Has part MHC Graphviz.jpg

Made new terms to enhance the function part of this graph:

Protein binding.jpg

The same has_part graph shown in tree form:

Has part MHC.jpg

The structure of the terms was based on pre-existing terms in the cellular component ontology:

Complex.jpg

Consequence of signal transmission

The group liked the changes that Sandra had suggested for the structure of "consequence of signal transmission" the previous week. Alex had many ideas for other child terms.

Action: Jennifer and Alex to meet and fill in these child terms.

Future plan:

Having comprehensively captured one path we made the following plan for work:

  • Define the terms fully.
  • Move the pre-existing signaling terms under our new top terms.
  • Fully document the changes so that other people will be able to add paths in future.
  • Propose to the Consortium that the graph should be made live.

14th December

Participants: Sandra Orchard, Peter D'Eustachio, Alex Diehl, Jennifer Deegan.

We moved all the pre-existing terms to fit them under our new structure.

The action items from last week are still outstanding so we aim to do these in the coming week.

Jennifer is to add standard definitions to the undefined terms where possible, and will them mail out to the participants the list of terms we have added to the graph over this entire project.

Once we have all had another look at these terms and their definitions, we hope to publicise the changes to the whole consortium after Christmas, with a view to making the terms live a few weeks later.