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The excerpt on Wired magazine of The Breakthrough by Charles Graeber has the following description of how James Allison found the T-cell receptor.

Suddenly it seemed so obvious: If Allision could rig up a way to compare B cells and T cells, devise a lab experiment that put one against the other and let their redundant surface proteins cancel each other out, the receptor should be the molecule that didn’t cancel out. Essentially, he was looking for a needle in a haystack, and his idea was to set fire to the haystack and sift the ashes—or as Allison puts it, “pick it out of the weeds.” Whatever was left would be the needle he was looking for.

It is a vivid metaphor. But the author does describe in more specific detail how the cancellation actually works. Can someone give such a description?

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Well so here's the paper, at least on Dr. Allison's side. Mind you, the discovery is shared by a number of individuals for their combined effort.

So what they did is took mice and immunized them with T-cell lymphoma cells. The mice would essentially produce B cells against the lymphoma cells. And so we know that B cells produce antibodies, and hybridoma methods exploit the B cells to get a lot of that antibody. With their constructed hybridoma library, they could look at reactivity of antibodies produced against the lymphoma cells against the reactivity of the same antibody against other cells. They ended up finding 1/43 antibodies, which they dubbed 124-4O, reacted to their lymphoma line, but not to other cells.

With a pull-down assay, they isolated the receptor and determined it was a heterodimeric glycoprotein. A step further, they looked at both B cells and T cells, then, and were able to detect similar structures in the T cells, but not in the B cells.

Someone correct me If I'm wrong, though.

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