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


Transmission




Consequence


Termination



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.

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.