Nature Immunol. doi:10.1038/ni.1768 (2009) Nature Immunol. doi:10.1038/ni.1766 (2009) Nature Immunol. doi:10.1038/ni.1769 (2009)

The maturation of pathogen-fighting T cells relies on a mysterious protein called Themis, three independent groups have found.

Themis is expressed exclusively in T cells, but its protein sequence — although highly conserved in vertebrates — provided few clues to its function. All three teams generated mouse mutants that lack the full-length Themis protein, and found that the usual process by which properly functioning T cells are selected to continue maturation in the thymus was impaired. The result: fewer T cells survived this selection, and the mice contained smaller numbers of mature T cells.

Paul Love of the National Institutes of Health in Bethesda, Maryland, and his colleagues found that this defect could be reversed by stimulating signalling through a protein complex called T-cell antigen receptor (TCR), which is crucial for the activation and development of T cells.

Meanwhile, a second group led by Nicholas Gascoigne of the Scripps Research Institute in La Jolla, California, demonstrated that signalling through the TCR mediated by two other key molecules — calcium and a protein called Erk — is reduced when Themis is lacking. And a team headed by Richard Cornall of the University of Oxford, UK, and Ronald Schwartz, also of the National Institutes of Health, found that the expression of several genes, including those involved in cell survival, was reduced in these mutants — possibly contributing to eventual T-cell death.