Self-MHC-restricted peptides recognized by an alloreactive T lymphocyte clone

Area of Science:

• Immunology
• Molecular Biology
• T cell biology

Background:

• Alloreactive T lymphocytes are detected in unprimed animals, suggesting cross-reactivity with foreign MHC.
• The prevailing hypothesis posits that self-MHC/peptide complexes mimic allo-MHC/peptide complexes, inducing T cell specificities.

Purpose of the Study:

• To identify self-MHC-restricted peptides that are recognized by T cell clones initially induced by allo-MHC.
• To provide evidence supporting the molecular mimicry hypothesis in T cell alloreactivity.

Main Methods:

• Generation of an allo-MHC-specific cytotoxic T lymphocyte (CTL) clone (2C) from H-2b mice.
• Positional scanning with random peptide libraries and an iterative approach to identify MHC-associated peptides.
• Inhibition experiments using MHC-specific antibodies to assess T cell receptor (TCR) recognition efficiency.

Main Results:

• The CTL clone 2C, specific for H-2Ld complexed with peptide LSPFPFDL, was characterized.
• A self-MHC-restricted peptide, SIYRYYGL, associated with H-2Kb, was identified as a ligand for the same TCR.
• Reciprocal cross-reactivity was observed: CTLs primed with SIYRYYGL responded to H-2Ld + LSPFPFDL, indicating shared structural features.

Conclusions:

• Self-MHC-peptide complexes can structurally mimic allo-MHC-peptide complexes, explaining T cell alloreactivity.
• The identified self-MHC-restricted peptides provide direct support for the molecular mimicry hypothesis in T cell responses to foreign MHC.