Structural basis of cytochrome c presentation by IE(k)

Area of Science:

• Immunology
• Structural Biology
• Biochemistry

Background:

• T cell antigens, specifically pigeon and moth cytochrome c peptides bound to mouse MHC class II (IE(k)), are extensively studied.
• Understanding peptide binding to MHC class II is crucial for deciphering immune responses.

Purpose of the Study:

• To elucidate the structural basis of peptide binding to mouse MHC class II (IE(k)) using crystal structures.
• To compare the binding of moth cytochrome c peptide and a variant pigeon cytochrome c peptide to IE(k).

Main Methods:

• X-ray crystallography was used to determine the structures of moth peptide-IE(k) and a variant pigeon peptide-IE(k) complexes.
• Analysis of peptide conformation and interactions within the MHC class II binding groove.

Main Results:

• The moth peptide and previously studied peptides bound to IE(k) feature a lysine at the p9 pocket.
• The pigeon peptide, with alanine at p9, adopts an extended conformation, shifting lysine to p10, unlike the kinking often seen in MHC class I peptide binding.
• A minor substitution (Ser for Thr) in the variant pigeon peptide resulted in significant changes in T cell recognition without apparent structural alteration.

Conclusions:

• Major histocompatibility complex class II imposes an extended peptide conformation, even when a conserved anchor residue is displaced.
• The determined structures provide insights into T cell receptor recognition and can interpret existing mutational studies of these ligands.