International Immunology, Vol 9, 249-261, Copyright © 1997 by Oxford University Press
FF Shih, DM Cerasoli and AJ Caton
Transgenic (Tg) mice expressing the influenza virus PR8 hemagglutinin (PR8
HA) were infected with PR8 virus and analyzed for their ability to generate
T cell responses to individual MHC class II-restricted T cell determinants
from the HA. HAmemb and HAtrunc mice each express HA transgene mRNA in many
tissues (including the thymus), but differ in the form and amount of the HA
that is expressed: HAmemb mice express the entire viral HA as a
membrane-bound neo-self antigen, whereas HAtrunc mice express lower levels
of a truncated HA polypeptide. HAmemb mice were found to mediate efficient
negative selection of autoreactive T cells directed to the major
I-Ed-restricted and I-Ad-restricted determinants from the HA (designated S1
and S2 respectively). S1- specific T cell responses were similarly
undetectable in PR8-infected HAtrunc mice. However, S2-specific T cells
were only partially eliminated in HAtrunc mice; indeed, even though their
frequency was reduced relative to non-Tg mice, S2-specific T cells still
constituted a sizable population in PR8-infected HAtrunc mice. Moreover,
the S2- specific T cells from HAtrunc and non-Tg mice appeared to be
equally sensitive to stimulation with S2 peptide, and in each case utilized
highly diverse T cell receptors to recognize S2-I-Ad. The findings
demonstrate that an individual class II-restricted T cell determinant can
be recognized as a cryptic self peptide during T cell repertoire formation
and as an immunodominant peptide in the context of an anti- viral T cell
response, providing a basis for the induction of autoreactive T cells by
viruses containing homologs of self antigens.
ARTICLES
A major T cell determinant from the influenza virus hemagglutinin (HA) can be a cryptic self peptide in HA transgenic mice
The Wistar Institute of Anatomy and Biology, Philadelphia, PA 19104, USA.
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