A TCR β-Chain Motif Biases toward Recognition of Human CD1 Proteins

Reinink, Peter, Shahine, Adam, Gras, Stephanie, Cheng, Tan-Yun, Farquhar, Rachel, Lopez, Kattya, Suliman, Sara A., Reijneveld, Josephine F., Le Nours, Jérôme, Tan, Li Lynn, León, Segundo R., Jimenez, Judith, Calderon, Roger, Lecca, Leonid, Murray, Megan B., Rossjohn, Jamie ORCID: https://orcid.org/0000-0002-2020-7522, Moody, D. Branch and Van Rhijn, Ildiko 2019. A TCR β-Chain Motif Biases toward Recognition of Human CD1 Proteins. Journal of Immunology 203 (12) , pp. 3395-3046. 10.4049/jimmunol.1900872

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Abstract

High-throughput TCR sequencing allows interrogation of the human TCR repertoire, potentially connecting TCR sequences to antigenic targets. Unlike the highly polymorphic MHC proteins, monomorphic Ag-presenting molecules such as MR1, CD1d, and CD1b present Ags to T cells with species-wide TCR motifs. CD1b tetramer studies and a survey of the 27 published CD1b-restricted TCRs demonstrated a TCR motif in humans defined by the TCR β-chain variable gene 4-1 (TRBV4-1) region. Unexpectedly, TRBV4-1 was involved in recognition of CD1b regardless of the chemical class of the carried lipid. Crystal structures of two CD1b-specific TRBV4-1+ TCRs show that germline-encoded residues in CDR1 and CDR3 regions of TRBV4-1–encoded sequences interact with each other and consolidate the surface of the TCR. Mutational studies identified a key positively charged residue in TRBV4-1 and a key negatively charged residue in CD1b that is shared with CD1c, which is also recognized by TRBV4-1 TCRs. These data show that one TCR V region can mediate a mechanism of recognition of two related monomorphic Ag-presenting molecules that does not rely on a defined lipid Ag.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Publisher:	American Association of Immunologists
ISSN:	0022-1767
Date of First Compliant Deposit:	12 March 2020
Date of Acceptance:	9 October 2019
Last Modified:	07 Nov 2022 09:49
URI:	https://orca.cardiff.ac.uk/id/eprint/130361

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