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The autoantibody repertoire: searching for order

Abstract

The spontaneously occurring autoantibodies that are associated with human diseases bear the hallmarks of a typical immune response. The repertoire of autoantibodies is surprisingly limited, however, and is the same in both humans and mice. Neither molecular mimicry nor immune dysregulation accounts for this unexpectedly narrow focus of specificities. Experimental data on the properties of the target autoantigens — such as their structure, catabolism, exposure to the immune system after cell death and recently described immunostimulatory effects on immature dendritic cells — indicate that these properties, in conjunction with the tissue microenvironment, help to select the autoantibody repertoire.

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Figure 1: Proposed path from a dying cell to the production of autoantibodies.

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Acknowledgements

I have had fruitful discussions with several colleagues on this subject, particularly L. Casciola-Rosen, P. Cohen, B. Eisenberg, R. Germain, Z. Howard, P. Lipsky, K. Nagaraju, J. Oppenheim, J. O'Shea, Judith Plotz, John Plotz, N. Raben, A. Rosen and R. Siegel.

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DATABASES

LocusLink

APRIL

asparaginyl-tRNA synthetase

aspartyl-tRNA synthetase

BAFF

CCR3

CCR5

CXCL8

EMAP2

histidyl-transfer RNA synthetase

lysyl-tRNA synthetase

Mer

seryl-tRNA synthetase

TLR9

tyrosyl-tRNA synthetase

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Plotz, P. The autoantibody repertoire: searching for order. Nat Rev Immunol 3, 73–78 (2003). https://doi.org/10.1038/nri976

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