Monthly Archives: October 2013


It was with great disgust that I read the account of Dr. Danielle Lee being a called an “urban whore” for not wanting to write for an obscure science blog since they didn’t offer financial compensation to their bloggers.

Misogyny AND racism! Well done, Biology-Online! You stay classy!

What makes this situation even worse is that Scientific American, where Dr. Lee blogs, forfeited a wonderful opportunity to create a teachable moment out of this, one that highlighted the discrimination that women in science face, and further scientists of colour face.  They deleted Dr. Lee’s post, in what seems to be a move to protect themselves from negative publicity, and, perhaps loss of revenue.

Think of how dehumanizing Biology-Online’s editor’s words are: “urban whore” robs Dr. Lee of the science that she does. It robs her of her mind, and unflinchingly places the focus on her body, as if to say that her intellectual contributions are equivalent to what a prostitute working a corner does.

Why the hate, I ask? Just because she asked for compensation? We live in a world where advances in the biological sciences are happening at breakneck speed, and where there is a need for stellar scientists, there is also a need for stellar scientist-communicators who can share the wonder and awe of research with the common populace. Dr. Lee is one such writer. Her posts are that rare tonic of witty and edifying. Shame! Shame on Biology-Online for reducing one so brilliant to a slab of meat that gets traded on an ugly marketplace, and shame on Scientific American for not standing by one of their finest.

Take care now,


Narcissus, A Natural Killer, and His Self-love

If you are an old-school immunologist, you will probably accuse me of sacrilege if I revealed the focus of my graduate work to you. You see, I work on and with an innate T-cell population called the Natural Killer T-cells, or NKT cells. Yes, you read that right. Innate T-cell. Deal with it!

NKT cells were discovered 20-ish years ago and so you know that they aren’t a fad. They are a distinct population of T-cells that have the NK1.1 (CD161) marker (associated with NK cells), and, while some may express a semi-invariant version of the TCR one associates with conventional αβ T-cells using the Vα24-Jα18 and Vβ11 TCR genes, for example, others (Type II NKT cells) have more variety in the kinds of T-cell receptors they express. Both Type I and Type II NKT cells distinguish themselves from conventional T-cells by being CD1d restricted (as opposed to the MHC restriction we’ve come to know and love, but only as delimited by its strict 8-11-amino-acid-linear-peptide criteria!). However, the two types of NKT cells distinguish themselves from each other via a weird-ass, sponge-born lipid called α-galactosylceramide, or alpha-galcer. Type II NKT cells don’t respond to alpha-galcer, while Type I’s do.

What I like about NKT cells is that they represent the best kind of immunocyte: the kind that bridges the gaps of communication between seemingly “pureblood” populations of innate and adaptive cells. That NKT cells can be autoreactive but also respond to foreign, potentially pathogenic antigens, that NKT cells can secrete signature Th1, Th2 and Th17 cytokines are all signs that this is a cell type that can swing both ways, or as many ways as there may be.

The element of narcissism that NKT cells seem to come with is also a major turn on for this young experimental scientist, You see, NKT cells can respond to self-antigens as well. The means of doing this are, quite frankly, awe-inspiring. It makes sense that the CD1d receptor has evolved to enable the α-linked microbial glycolipids to fit perfectly perpendicularly in its groove for effiicient antigen presentation to the NKT TCR. That the NKT TCR manages to flatten the β-linked mammalian antigens to fit it is nothing short of, well, unexpected, Mainly, because you’d expect the TCR to be the one to make the structural compromise, as it were. Is this something that NKT cells learn as they terminally differentiate? Is this the test that they have to pass in order to be selected for? The jury is still out…

Clearly, the implications of self-antigen reactivity are amazing in terms of the roles that NKT cells may play in graft rejection, anti-tumor immunity and immunomodulation. It also these very roles that define what exactly NKT cells do in the larger picture that is The Immune Response. Tracing the thymic development of NKT cells tells us that three distinct lineages of NKT cells exist (so far, anyway!): you have your T-bet hi, PLZF low, IFNγ and IL-4-producing, IL2R-expressing, CD4 +ve or -ve, NKR+, NKT1 cells; the transcription factor that dominates the NKT2 type cells is GATA3 and these cells are CD4+ and crank out IL-4 and IL-13, while bearing the IL17 receptor Rb. And, finally, the NKT17 type that are both CD4 and NKR negative and sweat IL-22 and IL17 and express receptors for IL-17 and IL-23. Sound familiar?

Just think! In a system of cells so geared towards specificity and an efficient division of the labour that is the immune response, there exists a population dedicated to fluidity in terms of the things they respond to and the phenotypes they subscribe to. NKT cells, to me, represent exactly what makes immunology work for me. If biochemistry and such as the Romance Languages, immunology is like English in that there are more exceptions to rules than there are adherents. It is a field that enables you to dream big, because everything is possible, though, at first, nothing makes sense!

Take care now,



We Don’t SMAC and Tell in This Business…

The number of T-helper subsets is staggering.  Well, staggering compared to the initial See-Saw* relationship we envisioned existing between the Th1 and Th2 profiles. A lot is known about these subsets, their hallmark cytokines, the transcription factors they couple with, and what musical genres really get them in a mood for proliferation…not really.

What is not known, however, shockingly, is what exactly initiates signaling at the T-cell Receptor (TCR)?  Weird, isn’t it? We got so caught up with all the drama in the middle of the story that we never bothered to ask how the story began?

The TCR is as elegantly put together and enigmatic as Don Draper. It is a membrane-spanning heterodimer made up of an elaborate, two-layered bow-tie  of β-pleated sheets: the classical immunoglobulin fold, as it were. The variable regions of this heterodimer, the Vα and the Vβ, interact via their bottom β-sheets. The constant regions also conform to the immunoglobulin fold but with one distinction: the top-most β-sheet of the Cα region is replaced by two linker-like strands. The significance of this pocket is not known. Yet.  The extra-cellular domain of the TCR has the aspect of the antigen-binding fragment (or Fab) region of an antibody molecule. That the extracellular domain of the TCR is what sidles up to the edges of a peptide-loaded MHC (pMHC) molecule to sample said peptide, this structural feature, so adept at recognition, makes a world of sense.

A co-conspirator of the TCR is CD3. Or rather, the four polypeptide chains(ε, γ, δ and ε)  that make up CD3.  Sort of the Roger Sterling to the TCR’s Don Draper, the intra-cellular regions of CD3 bear  Immunoreceptor Tyrosine-based Activation Motifs (ITAMs), the phosphorylation of which is one of early moments of signal transduction that activates a T-cell. In a lovingly rendered and thoroughly detailed treatment of how the TCR and CD3 fit together, Dr. Mike Kuhns of the University of Arizona (whom I’ve had the pleasure of dining with!) describes how the CD3δε and the CD3γε, in an “open face orientation”, dock on either side of the TCR. This not only provides evidence for there being sidedness for the TCR-CD3 complex, but also that the clustering of the complexes isn’t a random pile-up of multimeric complexes that orgiastically make signalling happen.

Ah, yes, the clustering! So much contention with the clustering. Are the TCR-CD3 clusters pre-assembled or do they huddle together once the TCR is activated? But as Xie et al tell us, in the T-cell’s self-communion, LAT (Linker of Activated T-cells) and TCR microclusters just lurk beneath the cell surface membrane, ready to co-mingle with CD3 when the time is right, and migrate to what becomes the inner circle of the cluster of receptors on the cell-surface: the central supramolecular activation cluster (cSMAC). The TCRs of the cSMAC are, themselves, bedizen with a cluster of accessory molecules like LFA-1 which form the peripheral SMAC or the pSMAC. In a conversation between antigen presenting cells and T-cells: these interactions ask the rather pivotal question of, “Shall we dance?” If the answer is “We shall!”, we might see some cytokine action!

Take care now,