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52–68 Structurally Related Self-Peptide(s) in I-E-Deficient Mice1
Section of Immunobiology and Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06510
The Y-Ae mAb and the 1H3.1 TCR-
ß (V1/Vß6)
are two immune receptors specific for I-Ab MHC class II
molecules complexed to the 52–68 fragment of the -chain of I-E
class II molecules (the E52–68 peptide). A profound
intrathymic negative selection occurs in 1H3.1 TCR transgenic mice in
the presence of an I-E transgene. The administration of mAbs to
1H3.1/I-E double-transgenic newborn mice reveals that
Y-Ae, but not the isotype-matched anti-I-E Y17 mAb,
rescues a significant number of mature
(Vß6highCD4+CD8-) thymocytes and
allows the detection of E52–68-reactive T cells in the
periphery. These observations indicate that deletion of autoreactive T
cells can be specifically inhibited in vivo by an mAb specific for the
deleting self-peptide:self-MHC class II complex. Similar inhibition
experiments indicate that C57BL/6
(I-Ab+/I-E-) mice constitutively express an
E-independent, Y-Ae-recognizable epitope(s). This
finding is confirmed by the phenotypic analysis of mature (MHC class II
high) C57BL/6 bone marrow-derived dendritic cells. Collectively, these
observations further illustrate the peptide specificity of negative
selection and demonstrate that MHC class II-positive cells from
unmanipulated C57BL/6 mice that lack a functional I-E gene can
assemble one or more self-peptide:I-Ab complexes
recognizable by the E52–68:I-Ab
complex-specific Y-Ae mAb.
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