Loss of Siglec expression on T lymphocytes during human evolution

Bibliographic Collection: 
CARTA-Inspired Publication, APE
Publication Type: Journal Article
Authors: Nguyen, D. H.; Hurtado-Ziola, N.; Gagneux, P.; Ajit Varki
Year of Publication: 2006
Journal: Proc Natl Acad Sci U S A
Volume: 103
Edition: 2006/05/10
Number: 20
Pagination: 7765-70
Date Published: May 16
Type of Article: Research Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov't
Publication Language: eng
ISBN Number: 0027-8424 (Print)0027-84
Accession Number: 16682635 PMID
Keywords: *Biological Evolution, Animals, Antigens, B-Lymphocytes/cytology/immunology, Calcium/metabolism, CD/*immunology, Cell Proliferation, Differentiation, Down-Regulation, Humans, Lectins/*immunology, Lymphocyte Activation, Myelomonocytic/*immunology

We report here that human T cells give much stronger proliferative responses to specific activation via the T cell receptor (TCR) than those from chimpanzees, our closest evolutionary relatives. Nonspecific activation using phytohemagglutinin was robust in chimpanzee T cells, indicating that the much lower response to TCR simulation is not due to any intrinsic inability to respond to an activating stimulus. CD33-related Siglecs are inhibitory signaling molecules expressed on most immune cells and are thought to down-regulate cellular activation pathways via cytosolic immunoreceptor tyrosine-based inhibitory motifs. Among human immune cells, T lymphocytes are a striking exception, expressing little to none of these molecules. In stark contrast, we find that T lymphocytes from chimpanzees as well as the other closely related "great apes" (bonobos, gorillas, and orangutans) express several CD33-related Siglecs on their surfaces. Thus, human-specific loss of T cell Siglec expression occurred after our last common ancestor with great apes, potentially resulting in an evolutionary difference with regard to inhibitory signaling. We confirmed this by studying Siglec-5, which is prominently expressed on chimpanzee lymphocytes, including CD4 T cells. Ab-mediated clearance of Siglec-5 from chimpanzee T cells enhanced TCR-mediated activation. Conversely, primary human T cells and Jurkat cells transfected with Siglec-5 become less responsive; i.e., they behave more like chimpanzee T cells. This human-specific loss of T cell Siglec expression associated with T cell hyperactivity may help explain the strikingly disparate prevalence and severity of T cell-mediated diseases such as AIDS and chronic active hepatitis between humans and chimpanzees.


Proc Natl Acad Sci U S A. 2006 May 16;103(20):7765-70. Epub 2006 May 8

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Alternate Journal: Proceedings of the National Academy of Sciences of the United States of America
Author Address:

Glycobiology Research and Training Center and Department of Medicine, University of California at San Diego, La Jolla, CA 92093, USA.

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