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Lipids hide or step aside for CD1-autoreactive T cell receptors

Cotton, Rachel N, Shahine, Adam, Rossjohn, Jamie and Moody, D Branch 2018. Lipids hide or step aside for CD1-autoreactive T cell receptors. Current Opinion in Immunology 52 , pp. 93-99. 10.1016/j.coi.2018.04.013

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Peptide and lipid antigens are presented to T cells when bound to MHC or CD1 proteins, respectively. The general paradigm of T cell antigen recognition is that T cell receptors (TCRs) co-recognize an epitope comprised of the antigen and antigen presenting molecule. Here we review the latest studies in which T cells operate outside the co-recognition paradigm: TCRs can broadly contact CD1 itself, but not the carried lipid. The essential structural feature in these new mechanisms is a large ‘antigen free’ zone on the outer surface of certain antigen presenting molecules. Whereas peptides dominate the exposed surface of MHC-peptide complexes, all human CD1 proteins have a closed, antigen-free surface, which is known as the A′ roof. These new structural models help to interpret recent biological studies of CD1 autoreactive T cells in vivo, which have now been broadly observed in studies on TCR-transgenic mice, healthy humans and patients with autoimmune disease.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Publisher: Elsevier
ISSN: 0952-7915
Last Modified: 22 Jul 2019 10:36

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