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Blood, Vol. 93 No. 3 (February 1), 1999:
pp. 952-962
Shaping the Repertoire of Cytotoxic T-Lymphocyte Responses:
Explanation for the Immunodominance Effect Whereby Cytotoxic T
Lymphocytes Specific for Immunodominant Antigens Prevent
Recognition of Nondominant Antigens
Stéphane Pion,
Gregory J. Christianson,
Pierre Fontaine,
Derry C. Roopenian, and
Claude Perreault
From the Research Center, Maisonneuve-Rosemont Hospital, Montreal,
Quebec, Canada; and The Jackson Laboratory, Bar Harbor, ME.
The immunodominance effect, whereby the presence of immunodominant
epitopes prevents recognition of nondominant determinants presented on
the same antigen-presenting cell (APC) considerably restricts the
repertoire of cytotoxic T lymphocyte (CTL) responses. To elucidate the
molecular basis of the immunodominance effect, we compared the
interactions of a dominant (B6dom1) and a nondominant
epitope (H-Y) with their restricting class I molecule
(H2-Db), and their ability to trigger cognate CTLs. We
found that B6dom1/Db complexes behaved as
optimal T-cell receptor (TCR) ligands and triggered a more rapid in
vivo expansion of cognate CTLs than H-Y/Db complexes. The
superiority of the dominant epitope was explained by its high cell
surface density (1,012 copies/cell for B6dom1 v 10 copies/cell for H-Y) and its optimal affinity for cognate TCRs. Based
on these results, we conclude that dominant class I-associated
epitopes are those that have optimal ability to trigger TCR signals in
CTLs. We propose that the rapid expansion of CTLs specific for dominant
antigens should enable them to compete more successfully than other
CTLs for occupancy of the APC surface.
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