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

Rachel N. Cotton, Adam Shahine, Jamie Rossjohn, D. Branch Moody

Research output: Contribution to journalReview ArticleResearchpeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)93-99
Number of pages7
JournalCurrent Opinion in Immunology
Volume52
DOIs
Publication statusPublished - 1 Jun 2018

Cite this

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abstract = "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.",
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Lipids hide or step aside for CD1-autoreactive T cell receptors. / Cotton, Rachel N.; Shahine, Adam; Rossjohn, Jamie; Moody, D. Branch.

In: Current Opinion in Immunology, Vol. 52, 01.06.2018, p. 93-99.

Research output: Contribution to journalReview ArticleResearchpeer-review

TY - JOUR

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AU - Shahine, Adam

AU - Rossjohn, Jamie

AU - Moody, D. Branch

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