Tynan, Fleur E., Burrows, Scott R., Buckle, Ashley M., Clements, Craig S., Borg, Natalie A., Miles, John J., Beddoe, Travis, Whisstock, James C., Wilce, Matthew C., Silins, Sharon L., Burrows, Jacqueline M., Kjer-Nielsen, Lars, Kostenko, Lyudmila, Purcell, Anthony W., McCluskey, James, and Rossjohn, Jamie (2005) T cell receptor recognition of a 'super-bulged' major histocompatibility complex class I–bound peptide. Nature Immunology, 6 (11). pp. 1114-1122.

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Abstract

Unusually long major histocompatibility complex (MHC) class I-restricted epitopes are important in immunity, but their 'bulged' conformation represents a potential obstacle to alphabeta T cell receptor (TCR)-MHC class I docking. To elucidate how such recognition is achieved while still preserving MHC restriction, we have determined here the structure of a TCR in complex with HLA-B(*)3508 presenting a peptide 13 amino acids in length. This complex was atypical of TCR-peptide-MHC class I interactions, being dominated at the interface by peptide-mediated interactions. The TCR assumed two distinct orientations, swiveling on top of the centrally bulged, rigid peptide such that only limited contacts were made with MHC class I. Although the TCR-peptide recognition resembled an antibody-antigen interaction, the TCR-MHC class I contacts defined a minimal 'generic footprint' of MHC-restriction. Thus our findings simultaneously demonstrate the considerable adaptability of the TCR and the 'shape' of MHC restriction.

Item ID:	45412
Item Type:	Article (Research - C1)
ISSN:	1529-2916
Funders:	National Health and Medical Research Council of Australia (NHMRC), Roche Organ Transplantation Research Fund, Australian Research Council (ARC)
Projects and Grants:	NHMRC Career Development Award, NHMRC Peter Doherty Training Fellowship
Date Deposited:	06 Sep 2016 23:31
FoR Codes:	11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110702 Applied Immunology (incl Antibody Engineering, Xenotransplantation and T-cell Therapies) @ 100%
SEO Codes:	92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920108 Immune System and Allergy @ 100%
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