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IgA1 presents both clonal and structural (dis)similarities within single donors serum and milk

ABSTRACT: The most abundant immunoglobulin present in the human body is IgA1. It has the highest concentrations at the mucosal lining and in biofluids such as milk and is the second most abundant class of antibodies in serum. We assessed the structural diversity and clonal repertoire of IgA1 containing molecular assemblies longitudinally in human serum and milk from three donors using a mass spectrometry-based approach. IgA-containing molecules purified from serum or milk were assessed by the release and subsequent analysis of the Fab fragments. Our data revealed that serum IgA1 consists of two distinct structural populations, namely monomeric IgA1 (80%) and dimeric joining (J-) chain coupled IgA1 (20%). Our data also confirmed that IgA1 in milk is present as SIgA, consisting of two (50%), three (33%) or four (17%) IgA1 molecules assembled with a J-chain and pIgR. Interestingly, the IgA1-Fab repertoire was distinct between the monomeric and the dimeric IgA1. The serum dimeric J-chain-coupled IgA1 repertoire contained several abundant clones also observed in the milk IgA1 repertoire. The latter had little to no overlap with the serum monomeric IgA1 repertoire. This suggests that human IgA1s have two distinct origins; one that produces dimeric J-chain-coupled IgA1 molecules that in human serum and milk, and another that produces monomeric IgA1 ending up exclusively in serum.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Albert J.R. Heck

PROVIDER: MSV000088915 | MassIVE | Thu Feb 24 09:27:00 GMT 2022

REPOSITORIES: MassIVE

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