What T cells see in B cells: Defining the immunopeptidome of germinal center B cells 2265788

Abstract Introduction Vaccine-induced germinal center reactions (GC) contain many B and T cells that display little measurable affinity for the immunogen, which is perplexing in late-stage GC reactions, when the quality of serum antibodies measured in the blood increases over time. I aim to addresses this disconnect by defining what T cells ‘see’ on B cells, by profiling the MHCII immunopeptidome of GC B cells. Methods This approach combines molecular immunology with mass spectrometry to profile what peptides are being presented on MHCII. Antibodies that recognize peptide-MHCII enable us to profile diverse antigens being presented overtime. Along with this, we will use pan-MHCII antibodies to pull down complexes, allowing mass spectrometric analysis of eluted peptide fractions. This can then be mapped back to their parental proteins to reconstruct the antigenic landscape available to T cells. Results I predict that late GC B cells will present a distinct catalogue of peptides, derived from many self-derived sources than early GC cells. This evolving peptide landscape may shape the ratio of helper and regulatory T cell interactions that GC B cells engage in over time, thereby influencing their selection. Conclusion This study will create the first longitudinal map of the GC B cell MHC-II immunopeptidome, showing how self-peptide presentation can shape the T cell compartment in the GC. Outcomes of this project will illuminate the black box of the GC and establish generalizable tools for the broader immunology community. Funding Source N/A Topic Categories Immune Response Regulation: Cellular Mechanisms (IRC)