Extracellular crosslinking mass spectrometry reveals HLA class I – HLA class II interactions on the cell surface

Human Leukocyte Antigen (HLA) complexes are critical cell-surface protein assemblies that facilitate T-cell surveillance of almost all cell types in the body. While receptor binding to HLA class I and II is well-described with detailed structural information, nature cis interactions within plasma membrane surveyed cells remains be better characterized, as protein-protein environment technically challenging profile. Here we performed extracellular chemical crosslinking on intact antigen presenting specifically elucidate present external membrane. We found crosslink dataset was dominated by inter- intra-protein crosslinks involving molecules, which enabled not only construction an HLA-centric interaction map, but also revealed multiple modes – further modeling based crosslinker distance restraints. Collectively, our data demonstrate molecules colocalize can densely packed