TY - JOUR
T1 - Positive selection is limited by available peptide-dependent MHC conformations
AU - Stefanski, Heather E.
AU - Jameson, Stephen C.
AU - Hogquist, Kristin A.
PY - 2000/4/1
Y1 - 2000/4/1
N2 - Recent data suggest that the diversity of self peptides presented in the thymus during development contributes to positive selection of a diverse T cell repertoire. We sought to determine whether a previously defined 'hole in the immunological repertoire' could be explained by the absence of an appropriate selecting self peptide. The repertoire defect in question is the inability of bm8 mice to make an H-2K-restricted response to OVA. Like other OVA-specific, H-2K-restricted receptors, OT-I-transgenic T cells are not positively selected in bm8 mice. Using criteria we had previously established for identifying positive selection ligands, we found peptides that could restore positive selection of OT-I thymocytes in bm8 mice. Thus, the T cell repertoire can be limited by a requirement for specific self peptides during development. Data with MHC-specific Abs suggested that peptides might be able to force MHC residues to adopt different conformations in K(b) vs K(bm8). This shows that peptides can potentially contribute to ligand diversity both directly (via variability in the solvent-exposed side chains) and indirectly (through their effect on the MHC conformation). Our data support a model where self peptide diversity allows selection of T cells specific for a broad range of MHC conformations.
AB - Recent data suggest that the diversity of self peptides presented in the thymus during development contributes to positive selection of a diverse T cell repertoire. We sought to determine whether a previously defined 'hole in the immunological repertoire' could be explained by the absence of an appropriate selecting self peptide. The repertoire defect in question is the inability of bm8 mice to make an H-2K-restricted response to OVA. Like other OVA-specific, H-2K-restricted receptors, OT-I-transgenic T cells are not positively selected in bm8 mice. Using criteria we had previously established for identifying positive selection ligands, we found peptides that could restore positive selection of OT-I thymocytes in bm8 mice. Thus, the T cell repertoire can be limited by a requirement for specific self peptides during development. Data with MHC-specific Abs suggested that peptides might be able to force MHC residues to adopt different conformations in K(b) vs K(bm8). This shows that peptides can potentially contribute to ligand diversity both directly (via variability in the solvent-exposed side chains) and indirectly (through their effect on the MHC conformation). Our data support a model where self peptide diversity allows selection of T cells specific for a broad range of MHC conformations.
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U2 - 10.4049/jimmunol.164.7.3519
DO - 10.4049/jimmunol.164.7.3519
M3 - Article
C2 - 10725706
AN - SCOPUS:0034176855
SN - 0022-1767
VL - 164
SP - 3519
EP - 3526
JO - Journal of Immunology
JF - Journal of Immunology
IS - 7
ER -