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Runner Up: T-cell tales

Science  20 Dec 1996:
Vol. 274, Issue 5295, pp. 1988
DOI: 10.1126/science.274.5295.1988e

T lymphocytes are one of the immune system's most potent weapons, directly triggering attacks on virus-infected cells. This year, a Nobel Prize went to the researchers who first began to describe how T cells recognize foreign antigens, and in a fitting complement, T cells also gave up their last great structural secret. In 1996, two independent groups managed to coax recalcitrant T cell receptor molecules to form crystals, allowing the first x-ray analysis of their 3D structure. And the teams captured the receptors in action—bound to their target molecules—offering new insight into how T cells learn to recognize their prey.

T cells depend on other cells to process foreign antigens into small peptides, which are then returned to the cell surface and displayed by proteins encoded by the major histocompatibility complex genes; the T cell then binds to the MHC protein complex. The new x-ray data clinch many previous predictions about this complex interaction and shed new light on exactly how the receptor aligns with the MHC molecule. Two rival orientations—orthogonal and congruent—had been predicted, but it turns out that neither is quite right: The receptor molecule finds a halfway house between them. This detailed knowledge helps pave the way to designing molecular therapies to jump-start the binding process in the many diseases where natural responses fail.

The T cells that bind.

A T cell receptor (blue) binds to MHC protein (red) and foreign peptide (yellow).

GARCIA ET AL.

ADDITIONAL READING

News Story:

  • R. F. Service, “Close-Up of a Killer,” Science, 11 October 1996, p. 176.

Research Papers:

  • D. N. Garboczi et al., Nature, 14 November 1996, p. 134-141.

  • K. C. Garcia et al., “An α βT Cell Receptor Structure at 2.5 Å and Its Orientation in the TCR-MHC Complex,” Science, 11 October 1996, p. 209.

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