A class of γδ T cell receptors recognize the underside of the antigen-presenting molecule MR1.
Jérôme Le NoursNicholas A GherardinSri H RamarathinamWael AwadFlorian WiedeBenjamin S GullyYogesh KhandokarT PraveenaJacinta M WubbenJarrod J SandowAndrew Ian WebbAnouk von BorstelMichael T RiceSamuel J RedmondRebecca SeneviratnaMaria L Sandoval-RomeroShihan LiMichael N T SouterSidonia B G EckleAlexandra J CorbettHugh H ReidLigong LiuDavid P FairlieEdward M GilesGlen P WestallRichard William TothillMartin S DaveyRichard BerryTony TiganisJames McCluskeyDaniel G PellicciAnthony Wayne PurcellAdam P UldrichDale I GodfreyJamie RossjohnPublished in: Science (New York, N.Y.) (2020)
T cell receptors (TCRs) recognize antigens presented by major histocompatibility complex (MHC) and MHC class I-like molecules. We describe a diverse population of human γδ T cells isolated from peripheral blood and tissues that exhibit autoreactivity to the monomorphic MHC-related protein 1 (MR1). The crystal structure of a γδTCR-MR1-antigen complex starkly contrasts with all other TCR-MHC and TCR-MHC-I-like complex structures. Namely, the γδTCR binds underneath the MR1 antigen-binding cleft, where contacts are dominated by the MR1 α3 domain. A similar pattern of reactivity was observed for diverse MR1-restricted γδTCRs from multiple individuals. Accordingly, we simultaneously report MR1 as a ligand for human γδ T cells and redefine the parameters for TCR recognition.