Lipids hide or step aside for CD1-autoreactive T cell receptors
RN Cotton, A Shahine, J Rossjohn… - Current opinion in …, 2018 - Elsevier
RN Cotton, A Shahine, J Rossjohn, DB Moody
Current opinion in immunology, 2018•ElsevierHighlights•Human CD1-autoreactive T cells are common and can mediate autoimmunity.•T
cell receptors can bind directly to CD1 without contacting bound lipid.•Lipids can hide buried
within the CD1 cleft.•Lipids can emerge toward the edge of CD1 and side step T cell
receptors.•CD1 autoreactivity is seen among αβ+, Vδ1+ and δ/αβ+ T cells.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 …
cell receptors can bind directly to CD1 without contacting bound lipid.•Lipids can hide buried
within the CD1 cleft.•Lipids can emerge toward the edge of CD1 and side step T cell
receptors.•CD1 autoreactivity is seen among αβ+, Vδ1+ and δ/αβ+ T cells.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 …
Highlights
- Human CD1-autoreactive T cells are common and can mediate autoimmunity.
- T cell receptors can bind directly to CD1 without contacting bound lipid.
- Lipids can hide buried within the CD1 cleft.
- Lipids can emerge toward the edge of CD1 and side step T cell receptors.
- CD1 autoreactivity is seen among αβ+, Vδ1+ and δ/αβ+ T cells.
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.
Elsevier
