15 February, 2010

Microcluster Condensation in Immunological Synapses 1

I remember reading one of the popular science magazines I subscribed to back in high school, probably either Popular Science or Discovery, and coming across a brief article on the discovery of the immunological synapse. It included pretty pictures. I was intrigued by the spatial and sequential alignment of disparate signaling effectors, even though I knew absolutely nothing about the context at the time. Now, I know more about the molecules and pathways involved in dendritic cell::T-cell signaling than I am able to concisely put down here in words without rolling myself up in a cloak of jargon, and even so I barely know anything (with comparison to both the experts in the field and the scale of the unresolved questions). The immunological synapse is fascinating, and to me it is beautiful in its absolute parsimony (that's a whole other post for later).

In beginning the activation of the adaptive immune system, dendritic cells process and present sampled antigen in distinct molecules (MHC) that T-cells can recognize (via the TCR and CD4/8). Due to chunk recombination of V, D, and J regions of the TCR binding motifs and subsequent pre-programmed random mutagenesis* there is extremely high heterogeneity in the recognition cognates of the TCRs. So as dendritic cells (DCs) crawl through the thymus, lymph node, spleen, or other, they have many distinct antigens loaded into their surface display molecules, and every once in a while a TCR that has some binding affinity for that antigen will bind. What follows is the immunological synapse.

The immunological synapse starts out with the binding of the TCR and CD4/8 to the MHC, which nucleate the formation of the central supramolecular activation complex (cSMAC), when all of the TCR/MHC complexes from microclusters and merge into 1 more stable site. A lot of other things happen downstream of that, most of which are very interesting**, but what I find intriguing about this is: what sort of topology do the kinetics of microcluster condensation add up to?

All optimized networks have some sort of topology. This means the hierarchy of one node over another, because to have all nodes processing the same exact bandwidth is rather energetically inefficient. As such, there can be strictly hierarchical topologies like those found inside human corporations with management, there can be scale-free topologies in which hierarchy arises due to through-put optimization and is not strict (a good example of this is the server structure of the Internet), or others I don't know anything about yet.

Is microcluster condensation hierarchical or scale-free?

Unfortunately, it is extremely difficult to answer that question empirically because it happens so fast and because the cells involved are rather camera-shy unless given very exacting and munificent conditions. Therefore, this is more or less a thought experiment.

I posit that microcluster condensation is both hierarchical and scale-free, in turn; first, hierarchical and then, later, scale-free. Cook your noodle on that for a bit, and I'll explain my reasoning for why within the next few days.

*Not a contradiction of terms. The immune system allows for random mutagenesis of a restricted set of amino acids residues on T-cell receptors and B-cell receptors to greatly increase the range of possible binding motifs without great additional informational storage costs (DNA).
**E.g., I find the activation of such factors as NFAT, mTOR, et al to be interesting, but generally find the dynamics of histone deacetlyation to be rather dull.


オテモヤン said...


quietandsmalladventures said...

actually i'm usually yawn inspired by the immune system, except that i used to love love love signaling (molecular dominoes!). i still love the one anomaly of the immunological synapse you didn't discuss: backdoor door attack on the MHC II and TCR by superantigens (maybe i love them because they're *super*?!) that lovely nonspecific interaction that activates loads of clonal t-cell populations and make someone horrendously ill :)

yeah, mad micro-/molecular biologist :)