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Different domains of β2-glycoprotein I play a role in autoimmune pathogenesis

Cellular & Molecular Immunology volume 17, pages 1210–1211 (2020)Cite this article

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The T-cell response to β2GPI observed in mouse models3 has been proposed to potentially be responsible for the spread of a B-cell epitope to multiple SLE-related autoantibodies4 since β2GPI binds to apoptotic cells,5 which express several SLE-associated autoantigens.6 Indeed, previous studies have demonstrated that a T-cell response to β2GPI is associated with a spread of multiple B-cell epitopes to SLE-related autoantibodies,7 although the epitope specificity of the β2GPI-specific T-cell response is determined by the MHC class II haplotype of an individual. Of note, one β2GPI T-cell epitope (peptide 23, NTGFYLNGADSAKCT) was shown to also be recognized by T cells from an HLA-DRB1*0403+ autoimmune patient, suggesting that the induced β2GPI-specific T-cell response mimics that in an autoimmune disease. These data suggested that the generation of a β2GPI-reactive T-cell response may be associated with the epitope spread to SLE-related autoantibodies, independently of the epitope specificity or MHC class II restriction. Thus, the generation of a β2GPI-reactive T-cell response has been hypothesized to represent a critical initiating event leading to a B-cell epitope spread, with consequent production of a wide range of SLE-related autoantibodies.

Salem and colleagues8 have evaluated the proliferative response of splenic T cells from mice with induced and spontaneous SLE to peptides spanning the entire sequence of the human β2GPI. They found that mice with induced and spontaneous SLE recognize a common T-cell epitope in domain III of β2GPI. β2GPI-reactive CD4+ T cells from the two models differed primarily in cytokine production: T cells from the mice with induced SLE expressed IFN-γ, whereas those from MRL/lpr mice expressed both IL-17 and IFN-γ. These data indicate that the generation of a β2GPI-reactive T-cell response is shared by both induced and spontaneous models of SLE and that this T-cell response may mediate the epitope spread to autoantibodies in both models.

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  1. Department of Experimental Medicine, University of Rome “La Sapienza”, viale Regina Elena 324, 00161, Rome, Italy

    Maurizio Sorice & Roberta Misasi

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  1. Maurizio Sorice
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  2. Roberta Misasi
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Sorice, M., Misasi, R. Different domains of β2-glycoprotein I play a role in autoimmune pathogenesis. Cell Mol Immunol 17, 1210–1211 (2020). https://doi.org/10.1038/s41423-018-0060-9

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