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J. Exp. Med.,
Volume 189, Number 3, February 1, 1999 483-491
By


From the * Department of Medical Microbiology and Immunology, Faculty of Medicine, University of
Alberta, Edmonton, Alberta T6G 2S2, Canada; and the Classical class I major histocompatibility complex (MHC) molecules, as well as the nonclassical
class I histocompatibility leukocyte antigen (HLA)-E molecule, can negatively regulate natural killer (NK) cell cytotoxicity through engagement of NK inhibitory receptors. We show that
expression of murine (m)CD1.1, a nonpolymorphic nonclassical MHC class I-like molecule
encoded outside the MHC, protects NK-sensitive RMA/S target cells from adherent lymphokine-activated killer cell (A-LAK) cytotoxicity. Passage of effector cells in recombinant interleukin (rIL)-2 enhanced protection by mCD1.1, suggesting an expansion of relevant A-LAK
population(s) or modulation of A-LAK receptor expression. Murine CD1.1 conferred protection from lysis by rIL-2-activated spleen cells of recombination activating gene (Rag)-1
La Jolla Institute for Allergy and Immunology,
San Diego, California 92121
/
mice,
which lack B and T cells, demonstrating that mCD1.1 can protect RMA/S cells from lysis by
NK cells. An antibody specific for mCD1.1 partially restored A-LAK lysis of RMA/S.CD1.1
transfectants, indicating that cell surface mCD1.1 can confer protection from lysis; therefore,
mCD1.1 possibly acts through interaction with an NK inhibitory receptor. CD1.1 is by far the
most divergent class I molecule capable of regulating NK cell activity. Finally, mCD1.1 expression rendered RMA/S cells resistant to lysis by A-LAK of multiple mouse strains. The conserved structure of mCD1.1 and pattern of mCD1.1 resistance from A-LAK lysis suggest that
mCD1.1 may be a ligand for a conserved NK inhibitory receptor.
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