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*
The Jackson Laboratory, Bar Harbor, ME 04609;
Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232; and
Division of Immunology Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720
Minor histocompatibility Ags (minor H Ags) are substantial
impediments to MHC-matched solid tissue and bone marrow
transplantation. From an antigenic standpoint, transplantation between
MHC-matched individuals has the potential to be remarkably complex. To
determine the extent to which the immune response is simplified by the
phenomenon of immunodominance, we used peptide/MHC tetramers based on
recently discovered minor H Ags (H60, H13, and HY) and monitored in
vivo CD8 T cell responses of female C57BL/6 mice primed with
MHC-matched, but background-disparate, male BALB.B cells. CD8 T cells
against H60 overwhelmed responses to the H13 and HY throughout primary
and secondary challenge. H60 immunodominance was an inherent quality,
overcoming a lower memory precursor frequency compared with that of H13
and evoking a T cell response with diverse TCRV
usage. IFN-
staining examining congenically defined minor H Ags extended H60
dominance over additional minor H Ags, H28, H4, and H7. These four
minor H Ags accounted for up to 85% of the CD8 T cell response, but
H60 stood out as the major contributor. These findings show that
immunodominance applies to antigenically complex transplantation
settings in vivo and that the responses to the H60 minor H Ag dominates
in this model. We suggest that immunodominant minor H Ags are those
that result from the absence of a self analog.
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