A Single Peptide–MHC Complex Positively Selects a Diverse and Specific CD8 T Cell Repertoire
Baomei Wang,1
Tina M. Primeau,1
Nancy Myers,1
Henry W. Rohrs,2
Michael L. Gross,2
Lonnie Lybarger,3
Ted H. Hansen,1
Janet M. Connolly1,*
Pathogen recognition by T cells is dependent on their exquisite
specificity for self–major histocompatibility complex
(MHC) molecules presenting a bound peptide. Although this specificity
results from positive and negative selection of developing T
cells in the thymus, the relative contribution of these two
processes remains controversial. To address the relation between
the selecting peptide-MHC complex and the specificity of mature
T cells, we generated transgenic mice that express a single
peptide–MHC class I complex. We demonstrate that positive
selection of CD8 T cells in these mice results in an MHC-specific
repertoire. Although selection on a single complex is peptide
promiscuous, mature T cells are highly peptide specific. Thus,
positive selection imparts MHC and peptide specificity on the
peripheral CD8 T cell repertoire.
2 Department of Chemistry, Washington University School of Medicine, St. Louis, MO 63110, USA.
3 Department of Cell Biology and Anatomy, University of Arizona, Tucson, AZ 85724, USA.
* To whom correspondence should be addressed. E-mail: connolly{at}wustl.edu
