Influence of protein-quaternary structure on antigen processing

Area of Science:

• Immunology
• Protein Structure and Function
• Molecular Biology

Background:

• T cell recognition is crucial for adaptive immunity.
• The quaternary structure of proteins can influence immune responses.
• Human chorionic gonadotropin (hCG) is a heterodimeric glycoprotein hormone.

Purpose of the Study:

• To analyze T cell recognition of the quaternary structure of human chorionic gonadotropin (hCG).
• To investigate how the association of hCG alpha (hCG-alpha) and beta (hCG-beta) subunits affects T cell epitope presentation.
• To determine the role of conformational changes versus primary structure in T cell recognition of hCG.

Main Methods:

• Production and characterization of hCG-alpha and hCG-beta specific T cell hybridomas in BALB/c mice.
• Fine specificity analysis of T cell hybridomas to map recognized epitopes.
• Kinetic experiments and experiments with homologous hormone dimers to assess the impact of quaternary structure on T cell recognition.

Main Results:

• hCG-alpha specific T cell hybridomas recognized distinct regions of the alpha subunit, with recognition significantly reduced for the hCG dimer compared to free hCG-alpha.
• hCG-beta specific T cell hybridomas showed comparable responses to free hCG-beta and the hCG dimer.
• The three-dimensional structure of the hCG complex, particularly conformational alterations in the alpha subunit upon dimerization, critically influenced T cell epitope processing and presentation.

Conclusions:

• Conformational changes in the alpha subunit due to quaternary structure formation primarily affect its T cell epitope processing.
• The beta subunit's processing and T cell epitope presentation are less affected by the quaternary structure of hCG.
• Protein quaternary structure can introduce novel elements in the understanding of oligomeric molecule processing and presentation to T cells.