I-Ep-bound self-peptides: identification, characterization, and role in alloreactivity

Area of Science:

• Immunology
• Molecular Biology
• Transplantation Science

Background:

• T cell recognition of peptide/MHC complexes drives transplant rejection.
• The roles of self-peptides and MHC molecules in alloreactivity are not fully understood.
• The specific self-peptide recognized by the 2.102 T cell clone in complex with I-Ep is unknown.

Purpose of the Study:

• To characterize peptides naturally presented by I-Ep.
• To define the binding motif for the murine I-Ep class II molecule.
• To identify specific allopeptides recognized by the 2.102 T cell clone.

Main Methods:

• Peptide characterization and binding motif determination for I-Ep.
• Bioinformatic search for candidate allopeptides using the I-Ep binding motif.
• T cell stimulation assays to validate candidate allopeptides.

Main Results:

• The I-Ep binding motif was defined, with a distinct P9 anchor residue preference.
• 19 identified self-peptides did not stimulate 2.102 T cells, indicating specificity.
• A G protein-coupled receptor 128 peptide was identified as a candidate allopeptide stimulating 2.102 T cells.

Conclusions:

• The G protein-coupled receptor 128 peptide is a candidate allopeptide specifically recognized by 2.102 T cells bound to I-Ep.
• Bioinformatics combined with experimental validation can identify specific allopeptides.
• Self-peptides play a specific role in alloreactivity and transplant rejection.