Structural insight into MR1-mediated recognition of the mucosal associated invariant T cell receptor
Rangsima Reantragoon, Lars Kjer-Nielsen, Onisha Patel, Zhenjun Chen, Patricia T Illing, Mugdha Bhati, Lyudmila Kostenko, Mandvi Bharadwaj, Bronwyn Meehan, Ted H Hansen, Dale I Godfrey, Jamie Rossjohn, James McCluskey
JOURNAL OF EXPERIMENTAL MEDICINE | ROCKEFELLER UNIV PRESS | Published : 2012
Mucosal-associated invariant T (MAIT) cells express a semiinvariant αβ T cell receptor (TCR) that binds MHC class I-like molecule (MR1). However, the molecular basis for MAIT TCR recognition by MR1 is unknown. In this study, we present the crystal structure of a human Vα7.2Jα33-Vβ2 MAIT TCR. Mutagenesis revealed highly conserved requirements for the MAIT TCR-MR1 interaction across different human MAIT TCRs stimulated by distinct microbial sources. Individual residues within the MAIT TCR β chain were dispensable for the interaction with MR1, whereas the invariant MAIT TCR α chain controlled specificity through a small number of residues, which are conserved across species and located within t..View full abstract
Awarded by NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
This work is supported by program and project grants of the Australian National Health and Medical Research Council (NHMRC). D.I. Godfrey is an NHMRC Senior Principal Research Fellow; J. Rossjohn is an Australia fellow of the NHMRC. R. Reantragoon is a PhD scholar funded by the Faculty of Medicine, Chulalongkorn University (Bangkok, Thailand) and by the King Chulalongkorn Memorial Hospital, Thai Red Cross.