Journal article
A T Cell Receptor Locus Harbors a Malaria-Specific Immune Response Gene
Immunity (Cambridge, Mass.), Vol.47(5), pp.835-847.e4
11/21/2017
DOI: 10.1016/j.immuni.2017.10.013
PMID: 29150238
Abstract
Immune response (Ir) genes, originally proposed by Baruj Benacerraf to explain differential antigen-specific responses in animal models, have become synonymous with the major histocompatibility complex (MHC). We discovered a non-MHC-linked Ir gene in a T cell receptor (TCR) locus that was required for CD8+ T cell responses to the Plasmodium berghei GAP5040-48 epitope in mice expressing the MHC class I allele H-2Db. GAP5040-48-specific CD8+ T cell responses emerged from a very large pool of naive Vβ8.1+ precursors, which dictated susceptibility to cerebral malaria and conferred protection against recombinant Listeria monocytogenes infection. Structural analysis of a prototypical Vβ8.1+ TCR-H-2Db-GAP5040-48 ternary complex revealed that germline-encoded complementarity-determining region 1β residues present exclusively in the Vβ8.1 segment mediated essential interactions with the GAP5040-48 peptide. Collectively, these findings demonstrated that Vβ8.1 functioned as an Ir gene that was indispensable for immune reactivity against the malaria GAP5040-48 epitope.
•P. berghei GAP5040-48-specific naive and memory CD8+ T cells uniformly express Vβ8.1•The GAP5040-48-specific CD8+ T cell response is entirely dependent on Vβ8.1•A large naive repertoire of GAP5040-48-specific CD8+ T cells is pathogenic in malaria•The Vβ8.1 gene-encoded CDR1β loop interacts directly with GAP5040-48
CD8+ T cells that recognize MHC I-peptide complexes contribute to protection or pathogenesis after infection. Van Braeckel-Budimir et al. demonstrate that a germline-encoded component of the T cell receptor functions as an Immune response (Ir) gene, controlling the CD8+ T cell response against a malaria epitope and the outcome of infection.
Details
- Title: Subtitle
- A T Cell Receptor Locus Harbors a Malaria-Specific Immune Response Gene
- Creators
- Natalija Van Braeckel-Budimir - Department of Microbiology, University of Iowa, Iowa City, IA 52242, USAStephanie Gras - Australian Research Council Centre of Excellence for Advanced Molecular Imaging, Monash University, Clayton, VIC 3800, AustraliaKristin Ladell - Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff CF14 4XN, UKTracy M Josephs - Australian Research Council Centre of Excellence for Advanced Molecular Imaging, Monash University, Clayton, VIC 3800, AustraliaLecia Pewe - Department of Microbiology, University of Iowa, Iowa City, IA 52242, USAStina L Urban - Department of Microbiology, University of Iowa, Iowa City, IA 52242, USAKelly L Miners - Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff CF14 4XN, UKCarine Farenc - Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, AustraliaDavid A Price - Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff CF14 4XN, UKJamie Rossjohn - Australian Research Council Centre of Excellence for Advanced Molecular Imaging, Monash University, Clayton, VIC 3800, AustraliaJohn T Harty - Department of Microbiology, University of Iowa, Iowa City, IA 52242, USA
- Resource Type
- Journal article
- Publication Details
- Immunity (Cambridge, Mass.), Vol.47(5), pp.835-847.e4
- Publisher
- Elsevier Inc
- DOI
- 10.1016/j.immuni.2017.10.013
- PMID
- 29150238
- ISSN
- 1074-7613
- eISSN
- 1097-4180
- Grant note
- DOI: 10.13039/100000002, name: National Institutes of Health (NIH), award: AI42767, AI85515, AI95178, AI100527, T32 AI007511, T32 AI007343; DOI: 10.13039/501100000923, name: Australian Research Council (ARC); DOI: 10.13039/501100000925, name: Australian National Health and Medical Research Council (NHMRC); DOI: 10.13039/100004440, name: Wellcome Trust, award: 100326/Z/12/Z; name: Monash Senior Research Fellow; DOI: 10.13039/100004440, name: Wellcome Trust Senior Investigator; DOI: 10.13039/501100000923, name: ARC Australian Laureate Fellow
- Language
- English
- Date published
- 11/21/2017
- Academic Unit
- University of Iowa; Pathology
- Record Identifier
- 9984047707702771
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