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The
Role of Lymphocyte Subtypes in Immunity 
Our laboratory is particularly interested in a subset of lymphocytes called
natural killer (NK) cells. NK cells spontaneously lyse certain tumor cells,
virally-infected cells, and hematopoietic blasts. They also can be stimulated
to produce cytokines, particularly gamma interferon, and this capacity
is important in regulating the nature of the T-cell immune response.
NK cells are of additional interest because they express cell-surface
receptors that interact with class I major histocompatibility antigens
and that either activate or inhibit NK cells. Individual NK cells express
different combinations of these receptors and thus differ in the specificity
with which they respond to, or are inhibited by, different target cells.
We have been studying (i) the molecular specificity of these receptors
and (ii) the signaling pathways by which the receptors either activate
or inhibit NK cells. For these studies, we have established in vitro cellular
models both for NK cells and for target cells that permit us to transfect
the former with specific receptors (wild-type or mutated) and the latter
with specific class I antigens (wild-type or mutated).This model has proved
fruitful in defining the specificities of NK cell receptors and the molecular
mechanisms by which they function.
Selected Publications:
Ryan, JC, Niemi, EC, Nakamura, MC and Seaman, WE. NKP-PIA is a target-specific
receptor that activates natural killer cell cytotoxicity. J Exp Med 181
(1995): 1911-5.
Nakamura, MC, Niemi, EC, Fisher, MJ, Schultz, LD, Seaman, WE, Ryan, JC.
Mouse Ly-49 interrupts early signaling events in NK cell cytotoxicity
and functionally associates with the SHP-1 tyrosine phosphatase. J Exp
Med 185 (1997): 673-84.
Ryan JC, Seaman WE. Divergent functions of lectin-like receptors on NK
cells. Immunol Rev 155 (1997):79-89.
Nakamura MC, Linnemeyer PA, Niemi EC, Mason LH, Ortaldo JR, Ryan JC, Seaman
WE. Mouse Ly-49D recognizes H-2Dd and activates natural killer cell cytotoxicity.
J Exp Med 189(1999):493-500.
Contact Information:
Email: seaman@itsa.ucsf.edu
Phone: 415/ 750-2037
Address: VAMC 111
The University of California, San Francisco, CA 94143, (415) 476-9000
Copyright 2003, The Regents of the University of California.
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