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Department of Immunology, Mayo Clinic, Rochester, MN 55905
Invariant chain (Ii) is a non-MHC-encoded molecule, which plays an
accessory role in the proper assembly/expression of functional MHC
class II molecules and there by plays an important role in Ag
processing/presentation. The phenotype of mice lacking Ii depends on
the allotype of the MHC class II molecule. In some mice strains, Ii
deficiency results in reduction in expression of class II molecules
accompanied by defective CD4+ T cell development. Responses
to conventional Ags/superantigens are also compromised. In this study,
we describe for the first time the functionality of human class II
molecules, HLA-DQ6 and HLA-DQ8, in transgenic mice lacking Ii. HLA
transgenic Ii-/- mice expressed very low levels of
surface DQ6 and DQ8 accompanied by severe reduction in CD4+
T cells both in the thymus and periphery. In vitro proliferation and
cytokine production to an exogenous superantigen, staphylococcal
enterotoxin B (SEB) was diminished in HLA-transgenic
Ii-/- mice. However, SEB-induced in vivo expansion of
CD8+ T cells expressing TCR V
8 family in
DQ8.Ii-/- mice was comparable with that of
DQ8.Ii+/+ mice. Systemic IFN-
production following in
vivo challenge with SEB was reduced in DQ8.Ii-/- mice and
were also protected from SEB-induced toxic shock. Although the T cell
response to a known peptide Ag was diminished in
DQ8.Ii-/- mice, DQ8.Ii-/- APCs were capable
of presenting that peptide to primed T cells from wild-type DQ8 mice as
well as to a specific T cell hybridoma. Differentiation of mature B
cells was also affected to a certain extent in DQ8.Ii-/-
mice.
This article has been cited by other articles:
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