Natalija Van Braeckel-Budimir1, Stephanie Gras2, Kristin Ladell3, Tracy M Josephs2, Lecia Pewe1, Stina L Urban1, Kelly L Miners3, Carine Farenc4, David A Price5, Jamie Rossjohn6, John T Harty7. 1. Department of Microbiology, University of Iowa, Iowa City, IA 52242, USA. 2. Australian Research Council Centre of Excellence for Advanced Molecular Imaging, Monash University, Clayton, VIC 3800, Australia; Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia. 3. Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff CF14 4XN, UK. 4. Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia. 5. Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff CF14 4XN, UK; Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA. Electronic address: priced6@cardiff.ac.uk. 6. Australian Research Council Centre of Excellence for Advanced Molecular Imaging, Monash University, Clayton, VIC 3800, Australia; Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia; Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff CF14 4XN, UK. Electronic address: jamie.rossjohn@monash.edu. 7. Department of Microbiology, University of Iowa, Iowa City, IA 52242, USA; Department of Pathology, University of Iowa, Iowa City, IA 52242, USA; Interdisciplinary Program in Immunology, University of Iowa, Iowa City, IA 52242, USA. Electronic address: john-harty@uiowa.edu.
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.
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 (n class="Gene">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 bergheiGAP5040-48 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 monocytogenesinfection. 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 malariaGAP5040-48 epitope.
Authors: Michelle A Neller; Kristin Ladell; James E McLaren; Katherine K Matthews; Emma Gostick; Johanne M Pentier; Garry Dolton; Andrea J A Schauenburg; Dan Koning; Ana Isabel C A Fontaine Costa; Thomas S Watkins; Vanessa Venturi; Corey Smith; Rajiv Khanna; Kelly Miners; Mathew Clement; Linda Wooldridge; David K Cole; Debbie van Baarle; Andrew K Sewell; Scott R Burrows; David A Price; John J Miles Journal: Immunol Cell Biol Date: 2015-03-24 Impact factor: 5.126
Authors: Samarchith P Kurup; Scott M Anthony; Lisa S Hancox; Rahul Vijay; Lecia L Pewe; Steven J Moioffer; Ramakrishna Sompallae; Chris J Janse; Shahid M Khan; John T Harty Journal: Cell Host Microbe Date: 2019-03-21 Impact factor: 21.023
Authors: Matthew D Martin; Isaac J Jensen; Andrew S Ishizuka; Mitchell Lefebvre; Qiang Shan; Hai-Hui Xue; John T Harty; Robert A Seder; Vladimir P Badovinac Journal: J Clin Invest Date: 2019-06-20 Impact factor: 19.456
Authors: Timothy P Riley; Lance M Hellman; Marvin H Gee; Juan L Mendoza; Jesus A Alonso; Kendra C Foley; Michael I Nishimura; Craig W Vander Kooi; K Christopher Garcia; Brian M Baker Journal: Nat Chem Biol Date: 2018-09-17 Impact factor: 15.040