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SUMMARY:LMB Seminar: What do we know about (your) antibodies? Novel insigh
 ts from novel techniques in mass spectrometry - Albert Heck\, University o
 f Utrecht\, The Netherlands
DTSTART:20230619T100000Z
DTEND:20230619T110000Z
UID:TALK194950@talks.cam.ac.uk
CONTACT:Scientific Meetings Co-ordinator
DESCRIPTION:1 Biomolecular Mass Spectrometry and Proteomics\, Bijvoet Cent
 er for Biomolecular Research and Utrecht Institute for Pharmaceutical Scie
 nces\, Utrecht University\, Padualaan 8\, 3584 CH Utrecht\, The Netherland
 s.\n2 Netherlands Proteomics Centre\, Padualaan 8\, 3584 CH Utrecht\, The 
 Netherlands.\nIn our body we produce every day huge amounts of antibodies\
 , of which many end up in circulation. It has been estimated that humans c
 an make about 1015 distinct antibody clones\, all exhibiting a slightly di
 fferent sequence. This huge number has so far refrained many from charting
  whole serum antibody\, or immunoglobulin (Ig)\, repertoires. We recently 
 developed an LC-MS based antibody repertoire profiling method for studying
  immunoglobulins in a quantitative manner.  We analyzed a variety of sampl
 es from both healthy as well as diseased donors and made some paradigm-shi
 fting observations. Firstly\, circulating Ig repertoires are much simpler 
 than anticipated\, dominated by a few hundred clones. Second\, the clonal 
 repertoires are entirely unique for each donor\, both for IgG1 and IgA1 we
  found virtually no overlap between individuals. Conversely\, longitudinal
  samples from the same (healthy) donor showed a far-reaching overlap even 
 when samples were taken months apart. In the repertoires of severely ill p
 atients\, more plasticity was observed. Charting the Ig repertoires in dis
 eased donors allowed the selection of Ig clones of interest\, i.e.\, those
  emerging after the onset of disease. We demonstrate that these latter ser
 um clones can be fully de novo sequenced by combining top-down and bottom-
 up analysis and iterative software algorithms to connect these layers of d
 ata. In this manner antigen-directed antibodies could be identified and de
 veloped into novel therapeutics.\nAll (sub)classes of immunoglobulins have
  unique structural features. In our work we also investigate the structure
 s of IgA1 and IgM\, and reveal that they are not always as described in te
 xt-books. I will present work through which we redefine the molecular comp
 osition of circulatory IgM. Using single-particle charge-detection mass sp
 ectrometry\, mass photometry\, proteomics\, and immunochemical assays\, we
  reveal that circulatory IgM is (re)defined by the universal presence of a
 n additional protein component. We study the covalent attachment of this p
 rotein and evaluate its effect on the binding of IgM to several receptors.
  Lastly\, our data reveal the distinctiveness of the circulatory and secre
 tory IgM
LOCATION:In person in the Max Perutz Lecture Theatre (CB2 0QH) and via Zoo
 m\, link: https://mrc-lmb-cam-ac-uk.zoom.us/j/92910980652?pwd=U2V6MGFOOU9k
 bmRnckNaU05HaXl4QT09
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