A Shared Gene-Expression Signature in Innate-Like Lymphocytes.

Innate and adaptive immunity are the two major arms of the immune system. They rely on very distinct cell-types, primarily distinguished by the source of diversity for non-self recognition, of germline or somatic origin. There exists, however, a subset of lymphocytes whose receptors require rearrangement but result in semi-invariant structures with a high degree of self-specificity. We hypothesized that these innate-like lymphocytes might share a common gene transcription signature. To test this notion, we made pair-wise comparisons of the gene-expression profiles of innate-like lymphocytes and closely paired adaptive system counterparts (NKT vs. CD4T, CD8ααT vs. CD8αβT, B1 vs. B2), and bioinformatically extracted common features and common genes distinguishing innate from adaptive cell-types. A statistically significant “innate signature” was indeed distilled, composed of a small set of genes over- and under-expressed in innate vs. adaptive lymphocytes. Particularly intriguing was the high representation of interferon-inducible GTPases crucial for resistance against intracellular pathogens, and of small G proteins involved in intracellular vacuole maturation and trafficking. Overall, this combined expression pattern can thus be designated as an “innate signature” among lymphocytes.