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-Induced MHC Class II Expression in Mice Lacking Class II Transactivator Due to Targeted Deletion of the GTP-Binding Domain1
*
Lineberger Comprehensive Cancer Center, and Departments of
Microbiology-Immunology and
Medicine, University of North Carolina, Chapel Hill, NC 27599; and
§
Department of Surgery, Duke University, Durham, NC 27710
Class II transactivator (CIITA) is an unusual transcriptional
coactivator in that it contains a functionally important, GTP-binding
consensus domain. To assess the functional role of the GTP-binding
domain of CIITA in vivo, we have generated knockout mice that bear a
mutation in the CIITA gene spanning the GTP-binding domain. Upon
analysis, these mice show no detectable CIITA mRNA; hence, they
represent mice with deleted CIITA rather than mice with defects in the
GTP-binding domain only. In these knockout mice, MHC class II
expression is nearly eliminated, although a faint RT-PCR signal is
visible in spleen, lymph node, and thymus, suggestive of the presence
of CIITA-independent regulation of MHC class II expression. Invariant
chain expression is also greatly reduced, but to a lesser extent than
MHC class II. Serum IgM is not decreased, but the serum IgG level is
greatly reduced, further confirming the absence of MHC class II
Ag-dependent Ig class switching. Induction of MHC class II expression
by IL-4 or LPS was absent on B cells, and Mac-1+ cells
showed no detectable induction of MHC class II by either IL-4, LPS, or
IFN-
. These findings demonstrate a requirement for CIITA in
IFN--, IL-4-, and endotoxin-induced MHC class II expression as well
as the possibility of rare CIITA-independent MHC class II
expression.
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