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J. Exp. Med.,
Volume 188, Number 5, September 7, 1998 867-876
24J
Q T Cell Receptor
Chains
By
§
From the * Department of Cancer Biology, Hematology/Oncology, Beth Israel-Deaconess Medical
Center, Boston, Massachusetts 02215; the A population of human T cells expressing an invariant V
Division of Rheumatology, Immunology, and Allergy,
Brigham and Women's Hospital, Boston, Massachusetts 02215; and the § Harvard Medical School,
Boston, Massachusetts 02115
24J
Q T cell antigen receptor
(TCR)
chain and high levels of CD161 (NKR-P1A) appears to play an immunoregulatory
role through production of both T helper (Th) type 1 and Th2 cytokines. Unlike other
CD161+ T cells, the major histocompatibility complex-like nonpolymorphic CD1d molecule
is the target for the TCR expressed by these T cells (V
24invt T cells) and by the homologous
murine NK1 (NKR-P1C)+ T cell population. In this report, CD161 was shown to act as a
specific costimulatory molecule for TCR-mediated proliferation and cytokine secretion by
V
24invt T cells. However, in contrast to results in the mouse, ligation of CD161 in the absence of TCR stimulation did not result in V
24invt T cell activation, and costimulation
through CD161 did not cause polarization of the cytokine secretion pattern. CD161 monoclonal antibodies specifically inhibited V
24invt T cell proliferation and cytokine secretion in
response to CD1d+ target cells, demonstrating a physiological accessory molecule function for
CD161. However, CD1d-restricted target cell lysis by activated V
24invt T cells, which involved a granule-mediated exocytotic mechanism, was CD161-independent. In further contrast to the mouse, the signaling pathway involved in V
24invt T cell costimulation through
CD161 did not appear to involve stable association with tyrosine kinase p56Lck. These results
demonstrate a role for CD161 as a novel costimulatory molecule for TCR-mediated recognition of CD1d by human V
24invt T cells.
24J
Q;
T cells
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