Siglec Expression on T Cells

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Human Uniqueness Compared to "Great Apes": 
Likely Difference
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CD33-related Siglecs are  signaling molecules that are expressed on most immune cells, and are mostly thought to downregulate cellular activation via cytosolic immunoreceptor tyrosine-based inhibitory motifs. Human T lymphocytes are a striking exception, expressing little to none of these receeptors. In striking contrast, T lymphocytes from “great apes” express several CD33-related Siglecs on their surfaces. This human-specific loss of T cell Siglec expression thus seems to have occurred after our last common ancestor with great apes, potentially causing a loss of inhibitory signaling. In keeping with this proposed "loss of brakes", human T cells give much stronger proliferative responses to specific activation via antibodies against the T cell receptor complex (a mimic of physiological activation), compared to those from chimpanzees. This human-specific loss of T cell CD33-related Siglec expression is associated with T cell hyperactivity, and may help explain the  apparently disparate prevalence and severity of T cell-mediated diseases between humans and chimpanzees


Timing of appearance of the difference in the Hominin Lineage as a defined date or a lineage separation event. The point in time associated with lineage separation events may change in the future as the scientific community agrees upon better time estimates. Lineage separation events are defined in 2017 as:

  • the Last Common Ancestor (LCA) of humans and old world monkeys was 25,000 - 30,000 thousand (25 - 30 million) years ago
  • the Last Common Ancestor (LCA) of humans and chimpanzees was 6,000 - 8,000 thousand (6 - 8 million) years ago
  • the emergence of the genus Homo was 2,000 thousand (2 million) years ago
  • the Last Common Ancestor (LCA) of humans and neanderthals was 500 thousand years ago
  • the common ancestor of modern humans was 100 - 300 thousand years ago

Definite Appearance: 
100 thousand years ago


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