Conformational changes in mouse MHC class II proteins at acidic pH.

Area of Science:

• Immunology
• Structural Biology

Background:

• MHC class II molecules present peptide antigens to T cells.
• Peptide-MHC class II interactions are regulated by pH, affecting binding and dissociation.
• Acidic pH enhances both peptide binding and dissociation from MHC class II.

Purpose of the Study:

• To investigate structural changes in MHC class II molecules at acidic pH.
• To determine if pH-induced structural modifications correlate with altered peptide association.

Main Methods:

• Circular dichroism spectroscopy was employed to study MHC class II structure.
• pH stability of A(d) and E(d) molecules was assessed across a range of pH values.

Main Results:

• MHC class II protein A(d) exhibited structural changes between pH 4 and 5, near the peptide binding optimum.
• More significant A(d) structural alterations occurred at lower pH, correlating with enhanced peptide dissociation.
• pH-induced structural changes in A(d) at pH 4-5 were reversible, but not at pH 3.
• Purified E(d) molecules showed altered structure only below pH 4, possibly due to endogenous peptide occupancy.

Conclusions:

• MHC class II structure is sensitive to pH, influencing peptide binding and dissociation dynamics.
• Reversible structural changes at moderately acidic pH (4-5) modulate peptide interaction.
• Irreversible structural changes at lower pH impact MHC class II function in T cell recognition.