The molecular basis for recognition of CD1d/α-galactosylceramide by a human non-Vα24 T cell receptor.

CD1d-mediated presentation of glycolipid antigens to T cells is capable of initiating powerful immune responses that can have a beneficial impact on many diseases. Molecular analyses have recently detailed the lipid antigen recognition strategies utilized by the invariant Vα24-Jα18 TCR rearrangement...

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Autores principales:	Jacinto López-Sagaseta, Jennifer E Kung, Paul B Savage, Jenny Gumperz, Erin J Adams
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/1d5f5e67e99f4a09827592cf96ca8a57
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spelling	oai:doaj.org-article:1d5f5e67e99f4a09827592cf96ca8a572021-11-18T05:37:23ZThe molecular basis for recognition of CD1d/α-galactosylceramide by a human non-Vα24 T cell receptor.1544-91731545-788510.1371/journal.pbio.1001412https://doaj.org/article/1d5f5e67e99f4a09827592cf96ca8a572012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23109910/pdf/?tool=EBIhttps://doaj.org/toc/1544-9173https://doaj.org/toc/1545-7885CD1d-mediated presentation of glycolipid antigens to T cells is capable of initiating powerful immune responses that can have a beneficial impact on many diseases. Molecular analyses have recently detailed the lipid antigen recognition strategies utilized by the invariant Vα24-Jα18 TCR rearrangements of iNKT cells, which comprise a subset of the human CD1d-restricted T cell population. In contrast, little is known about how lipid antigens are recognized by functionally distinct CD1d-restricted T cells bearing different TCRα chain rearrangements. Here we present crystallographic and biophysical analyses of α-galactosylceramide (α-GalCer) recognition by a human CD1d-restricted TCR that utilizes a Vα3.1-Jα18 rearrangement and displays a more restricted specificity for α-linked glycolipids than that of iNKT TCRs. Despite having sequence divergence in the CDR1α and CDR2α loops, this TCR employs a convergent recognition strategy to engage CD1d/αGalCer, with a binding affinity (∼2 µM) almost identical to that of an iNKT TCR used in this study. The CDR3α loop, similar in sequence to iNKT-TCRs, engages CD1d/αGalCer in a similar position as that seen with iNKT-TCRs, however fewer actual contacts are made. Instead, the CDR1α loop contributes important contacts to CD1d/αGalCer, with an emphasis on the 4'OH of the galactose headgroup. This is consistent with the inability of Vα24- T cells to respond to α-glucosylceramide, which differs from αGalCer in the position of the 4'OH. These data illustrate how fine specificity for a lipid containing α-linked galactose is achieved by a TCR structurally distinct from that of iNKT cells.Jacinto López-SagasetaJennifer E KungPaul B SavageJenny GumperzErin J AdamsPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Biology, Vol 10, Iss 10, p e1001412 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Jacinto López-Sagaseta Jennifer E Kung Paul B Savage Jenny Gumperz Erin J Adams The molecular basis for recognition of CD1d/α-galactosylceramide by a human non-Vα24 T cell receptor.
description	CD1d-mediated presentation of glycolipid antigens to T cells is capable of initiating powerful immune responses that can have a beneficial impact on many diseases. Molecular analyses have recently detailed the lipid antigen recognition strategies utilized by the invariant Vα24-Jα18 TCR rearrangements of iNKT cells, which comprise a subset of the human CD1d-restricted T cell population. In contrast, little is known about how lipid antigens are recognized by functionally distinct CD1d-restricted T cells bearing different TCRα chain rearrangements. Here we present crystallographic and biophysical analyses of α-galactosylceramide (α-GalCer) recognition by a human CD1d-restricted TCR that utilizes a Vα3.1-Jα18 rearrangement and displays a more restricted specificity for α-linked glycolipids than that of iNKT TCRs. Despite having sequence divergence in the CDR1α and CDR2α loops, this TCR employs a convergent recognition strategy to engage CD1d/αGalCer, with a binding affinity (∼2 µM) almost identical to that of an iNKT TCR used in this study. The CDR3α loop, similar in sequence to iNKT-TCRs, engages CD1d/αGalCer in a similar position as that seen with iNKT-TCRs, however fewer actual contacts are made. Instead, the CDR1α loop contributes important contacts to CD1d/αGalCer, with an emphasis on the 4'OH of the galactose headgroup. This is consistent with the inability of Vα24- T cells to respond to α-glucosylceramide, which differs from αGalCer in the position of the 4'OH. These data illustrate how fine specificity for a lipid containing α-linked galactose is achieved by a TCR structurally distinct from that of iNKT cells.
format	article
author	Jacinto López-Sagaseta Jennifer E Kung Paul B Savage Jenny Gumperz Erin J Adams
author_facet	Jacinto López-Sagaseta Jennifer E Kung Paul B Savage Jenny Gumperz Erin J Adams
author_sort	Jacinto López-Sagaseta
title	The molecular basis for recognition of CD1d/α-galactosylceramide by a human non-Vα24 T cell receptor.
title_short	The molecular basis for recognition of CD1d/α-galactosylceramide by a human non-Vα24 T cell receptor.
title_full	The molecular basis for recognition of CD1d/α-galactosylceramide by a human non-Vα24 T cell receptor.
title_fullStr	The molecular basis for recognition of CD1d/α-galactosylceramide by a human non-Vα24 T cell receptor.
title_full_unstemmed	The molecular basis for recognition of CD1d/α-galactosylceramide by a human non-Vα24 T cell receptor.
title_sort	molecular basis for recognition of cd1d/α-galactosylceramide by a human non-vα24 t cell receptor.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/1d5f5e67e99f4a09827592cf96ca8a57
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The molecular basis for recognition of CD1d/α-galactosylceramide by a human non-Vα24 T cell receptor.

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