A T cell receptor locus harbors a malaria-specific immune response gene

Van Braeckel-Budimir, Natalija, Gras, Stephanie, Ladell, Kristin ORCID: https://orcid.org/0000-0002-9856-2938, Josephs, Tracy M., Pewe, Lecia, Urban, Stina L., Miners, Kelly L., Farenc, Carine, Price, David A. ORCID: https://orcid.org/0000-0001-9416-2737, Rossjohn, Jamie ORCID: https://orcid.org/0000-0002-2020-7522 and Harty, John T. 2017. A T cell receptor locus harbors a malaria-specific immune response gene. Immunity 47 (5) , 835-847.e4. 10.1016/j.immuni.2017.10.013

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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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Publisher:	Elsevier (Cell Press)
ISSN:	1074-7613
Date of First Compliant Deposit:	20 March 2018
Date of Acceptance:	26 October 2017
Last Modified:	15 Nov 2024 15:00
URI:	https://orca.cardiff.ac.uk/id/eprint/109926

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