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Science 5 November 1993:
Vol. 262. no. 5135, pp. 907 - 909
DOI: 10.1126/science.7694362
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Articles

Science, Vol 262, Issue 5135, 907-909
Copyright © 1993 by American Association for the Advancement of Science

articles

Uncovering of functional alternative CTLA-4 counter-receptor in B7-deficient mice

GJ Freeman, F Borriello, RJ Hodes, H Reiser, KS Hathcock, G Laszlo, AJ McKnight, J Kim, L Du, DB Lombard, and al. et

Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, MA.

B7 delivers a costimulatory signal through CD28, resulting in interleukin-2 secretion and T cell proliferation. Blockade of this pathway results in T cell anergy. The in vivo role of B7 was evaluated with B7-deficient mice. These mice had a 70 percent decrease in costimulation of the response to alloantigen. Despite lacking B7 expression, activated B cells from these mice bound CTLA-4 and GL1 monoclonal antibody, demonstrating that alternative CTLA-4 ligand or ligands exist. These receptors are functionally important because the residual allogenic mixed lymphocyte responses were blocked by CTLA4Ig. Characterization of these CTLA-4 ligands should lead to strategies for manipulating the immune response.


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