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Unconventional recognition of peptides by T cells and the implications for autoimmunity

Abstract

The interaction of antigen-presenting cells with free peptides or a denatured protein can give rise to peptide–MHC class II complexes that are distinct from those generated after the processing of the whole protein. Such atypical peptide–MHC complexes can be recognized by unconventional 'type B' T cells that are not a component of the normal immune response to proteins. Importantly, these unconventional T cells can be found in the setting of autoimmunity. Here, we discuss unconventional peptide recognition by type B T cells and consider the implications for type 1 diabetes and other autoimmune diseases.

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Figure 1: Cellular pathways of antigen processing and presentation.
Figure 2: Self-reactive type B T cells routinely escape negative selection.
Figure 3: The presentation of peptides to self-reactive type B T cells.

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Acknowledgements

We are grateful to our many colleagues who contributed to the work cited here. They include B. Calderon, J. Carrero, K. Chang, M. Gross, J. Herzog, M. Levisetti, S. Lovitch, M. Miller, S. Petzold, Z. Pu and B. Strong. Our work was supported by grants from the US National Institutes of Health, the Juvenile Diabetes Research Foundation and the Kilo Diabetes and Vascular Research Foundation.

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Mohan, J., Unanue, E. Unconventional recognition of peptides by T cells and the implications for autoimmunity. Nat Rev Immunol 12, 721–728 (2012). https://doi.org/10.1038/nri3294

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