Unconventional T Cells: Fundamental Biology and Therapeutic Potential

Preclinical development of a cross-protective β-SARS-CoV-2 virus-like particle vaccine adjuvanted with MF59

L Earnest, DF Ruiz, MA Edeling, JC Montoya, AHY Yap, CY Wong, LE Holz, S Gras, S Collett, JP Cooney, KC Davidson, SL Grimley, DFJ Purcell, J Roberts, J Mumford, CW Tan, LF Wang, DI Godfrey, M Frieman, D Hans

2026-12-01

Whilst COVID vaccines proved to be effective in preventing severe COVID disease, they failed to control the emergence of variant v..

Sideways lipid presentation by the antigen-presenting molecule CD1c

TP Cao, GR Liao, TY Cheng, Y Chen, L Ciacchi, TS Fulford, R Farquhar, J Kollmorgen, JA Mayfield, AP Uldrich, EZQ Ng, GS Ogg, DI Godfrey, NA Gherardin, YL Chen, DB Moody, A Shahine, J Rossjohn

2026-12-01

For the MHC, MR1 and CD1 systems, antigen recognition involves contact of the membrane distal surfaces of both the αβ T cell recep..

The NF-κB transcription factor RelA directs mucosal-associated invariant T-cell development

TS Fulford, HF Koay, R Grumont, DN Johnson, S Scheer, HJ Nel, R Thomas, JYW Mak, DP Fairlie, CE Teh, DHD Gray, VL Bryant, C Zaph, LA O'Reilly, S Gerondakis, DI Godfrey

2026-04-01

Mucosal-associated invariant T (MAIT) cells are characterized by rapid responses to nonpeptide antigens via invariant T-cell recep..

Specific targeting of MR1-antigen complexes using nanobodies.

MH Shakir Hussain, Samuel J Redmond, Wael Awad, Calvin Xu, Caroline Soliman, Lisa Ciacchi, Alexis P Gonzalez, Jeffrey YW Mak, David P Fairlie, James McCluskey, Adam P Uldrich, Jamie Rossjohn, Dale I Godfrey, Hui-Fern Koay, Nicholas A Gherardin

2026-03-25

UNLABELLED: T cell receptor mimic (TCRm) antibodies and nanobodies that specifically bind peptide-HLA complexes have great therape..

Antibody-like recognition of a γδ T cell receptor toward a foreign antigen

L Rashleigh, H Venugopal, MT Rice, SD Gunasinghe, CL Sok, NA Gherardin, CF Almeida, I Van Rhijn, DB Moody, DI Godfrey, J Rossjohn, BS Gully

2025-10-02

The antigen recognition principles of B cells and αβ T cells have been well described compared to those of the γδ T cell. By way o..

Spectroscopic Characterization and Differentiation of SARS-CoV-2 Virus-like Particles

A Dodla, M Giergiel, A Mclean, K Kochan, L Earnest, MA Edeling, JL McAuley, DI Godfrey, DFJ Purcell, AHY Yap, JC Montoya, JA Roberts, S Collett, S Shukla, S Saxena, J Torresi, BR Wood

2025-08-19

Virus-like particles (VLPs) are recombinant, noninfectious, self-assembled structures that are made up of the viral structural pro..

A molecular basis underpinning TRBV28 T-cell receptor recognition of MR1–antigen

W Awad, NA Gherardin, L Ciacchi, AN Keller, L Liu, DP Fairlie, J McCluskey, DI Godfrey, J Rossjohn

2025-08-01

Mucosal-associated invariant T (MAIT) cells express a TRAV1-2⁺ T-cell receptor (TCR) that recognizes microbial vitamin ..

An unconventional T cell nexus drives HCK-mediated chronic obstructive pulmonary disease in mice

AT Hsu, RJJ O'Donoghue, E Tsantikos, TA Gottschalk, JG Borger, NA Gherardin, C Xu, HF Koay, DI Godfrey, M Ernst, GP Anderson, ML Hibbs

2025-05-01

Background: Chronic obstructive pulmonary disease (COPD) is a heterogeneous inflammatory lung disease leading to progressive, dest..

mRNA vaccines encoding membrane-anchored RBDs of SARS-CoV-2 mutants induce strong humoral responses and can overcome immune imprinting

Hareth A Al-Wassiti, Stewart A Fabb, Samantha L Grimley, Ruby Kochappan, Joan K Ho, Chinn Yi Wong, Chee Wah Tan, Thomas J Payne, Asuka Takanashi, Chee Leng Lee, Rekha Shandre Mugan, Horatio Sicilia, Serena LY Teo, Julie McAuley, Paula Ellenberg, James P Cooney, Kathryn C Davidson, Richard Bowen, Marc Pellegrini, Steven Rockman

2024-12-12

We investigated mRNA vaccines encoding a membrane-anchored receptor-binding domain (RBD), each a fusion of a variant RBD, the tran..

Selective regulation of IFN-γ and IL-4 co-producing unconventional T cells by purinergic signaling

C Xu, A Obers, M Qin, A Brandli, J Wong, X Huang, A Clatch, A Fayed, G Starkey, R D’costa, CL Gordon, JYW Mak, DP Fairlie, L Beattie, LK Mackay, DI Godfrey, HF Koay

2024-12-02

Unconventional T cells, including mucosal-associated invariant T (MAIT), natural killer T (NKT), and gamma-delta T (γδT) cells, co..

Direct recognition of an intact foreign protein by an αβ T cell receptor

CF Almeida, BS Gully, CM Jones, L Kedzierski, SD Gunasinghe, MT Rice, R Berry, NA Gherardin, TT Nguyen, YF Mok, JF Reijneveld, DB Moody, I Van Rhijn, NL La Gruta, AP Uldrich, J Rossjohn, DI Godfrey

2024-12-01

αβ T cell receptors (αβTCRs) co-recognise antigens when bound to Major Histocompatibility Complex (MHC) or MHC class I-like molecu..

Transiently boosting Vγ9 Vδ2 γδ T cells early in Mtb coinfection of SIV-infected juvenile macaques does not improve Mtb host resistance

EC Larson, AL Ellis, MA Rodgers, AK Gubernat, JL Gleim, RV Moriarty, AJ Balgeman, YT de Menezes, CL Ameel, DJ Fillmore, SM Pergalske, JA Juno, P Maiello, HB Chishti, PL Lin, DI Godfrey, SJ Kent, DG Pellicci, LC Ndhlovu, SL O'Connor

2024-12-01

Children living with HIV have a higher risk of developing tuberculosis (TB), a disease caused by the bacterium Mycobacterium tuber..

Impaired endocytosis and accumulation in early endosomal compartments defines herpes simplex virus–mediated disruption of the nonclassical MHC class I–related molecule MR1

C Samer, HEG McWilliam, BP McSharry, JG Burchfield, RJ Stanton, J Rossjohn, JA Villadangos, A Abendroth, B Slobedman

2024-10-01

Presentation of metabolites by the major histocompatibility complex class I–related protein 1 (MR1) molecule to mucosal-associated..

Lipidomic scanning of self-lipids identifies headless antigens for natural killer T cells

Tan-Yun Cheng, T Praveena, Srinath Govindarajan, Catarina F Almeida, Daniel G Pellicci, Wellington C Arkins, Ildiko Van Rhijn, Koen Venken, Dirk Elewaut, Dale I Godfrey, Jamie Rossjohn, D Branch Moody

2024-08-01

To broadly measure the spectrum of cellular self-antigens for natural killer T cells (NKT), we developed a sensitive lipidomics sy..

Vγ9Vδ2 T cells recognize butyrophilin 2A1 and 3A1 heteromers

TS Fulford, C Soliman, RG Castle, M Rigau, Z Ruan, O Dolezal, R Seneviratna, HG Brown, E Hanssen, A Hammet, S Li, SJ Redmond, A Chung, MA Gorman, MW Parker, O Patel, TS Peat, J Newman, A Behren, NA Gherardin

2024-08-01

Butyrophilin (BTN) molecules are emerging as key regulators of T cell immunity; however, how they trigger cell-mediated responses ..

Preclinical evaluation of therapeutic vaccines for chronic hepatitis B that stimulate antiviral activities of T cells and NKT cells

AH Mooney, SL Draper, OK Burn, RJ Anderson, BJ Compton, C Tang, KJ Farrand, P Di Lucia, M Ravà, V Fumagalli, L Giustini, E Bono, DI Godfrey, WR Heath, W Yuan, FV Chisari, LG Guidotti, M Iannacone, J Sidney, A Sette

2024-05-01

Background & Aims: Liver diseases resulting from chronic HBV infection are a significant cause of morbidity and mortality. Vaccine..

Multi-targeted loss of the antigen presentation molecule MR1 during HSV-1 and HSV-2 infection

C Samer, HEG McWilliam, BP McSharry, T Velusamy, JG Burchfield, RJ Stanton, DC Tscharke, J Rossjohn, JA Villadangos, A Abendroth, B Slobedman

2024-02-16

The major histocompatibility complex (MHC), Class-I-related (MR1) molecule presents microbiome-synthesized metabolites to Mucosal-..

Enhanced CD1d phosphatidylserine presentation using a single-domain antibody promotes immunomodulatory CD1d-TIM-3 interactions

R Lameris, A Shahine, M Veth, B Westerman, DI Godfrey, DL Hulsik, P Brouwer, J Rossjohn, TD de Gruijl, HJ van der Vliet

2023-12-01

Background CD1d is a monomorphic major histocompatibility complex class I-like molecule that presents lipid antigens to distinct T..

Interim results from a phase I randomized, placebo-controlled trial of novel SARS-CoV-2 beta variant receptor-binding domain recombinant protein and mRNA vaccines as a 4th dose booster

TM Nolan, G Deliyannis, M Griffith, S Braat, LF Allen, J Audsley, AW Chung, M Ciula, NA Gherardin, ML Giles, TP Gordon, SL Grimley, L Horng, DC Jackson, JA Juno, K Kedzierska, SJ Kent, SR Lewin, M Littlejohn, HA McQuilten

2023-12-01

Background: SARS-CoV-2 booster vaccination should ideally enhance protection against variants and minimise immune imprinting. This..

Newborn and child-like molecular signatures in older adults stem from TCR shifts across human lifespan

Carolien E van de Sandt, Thi HO Nguyen, Nicholas A Gherardin, Jeremy Chase Crawford, Jerome Samir, Anastasia A Minervina, Mikhail V Pogorelyy, Simone Rizzetto, Christopher Szeto, Jasveen Kaur, Nicole Ranson, Sabrina Sonda, Alice Harper, Samuel J Redmond, Hayley A McQuilten, Tejas Menon, Sneha Sant, Xiaoxiao Jia, Kate Pedrina, Theo Karapanagiotidis

2023-11-01

CD8⁺ T cells provide robust antiviral immunity, but how epitope-specific T cells evolve across the human lifespan is un..

Broad immunity to SARS-CoV-2 variants of concern mediated by a SARS-CoV-2 receptor-binding domain protein vaccine

G Deliyannis, NA Gherardin, CY Wong, SL Grimley, JP Cooney, SJ Redmond, P Ellenberg, KC Davidson, FL Mordant, T Smith, M Gillard, E Lopez, J McAuley, CW Tan, JJ Wang, W Zeng, M Littlejohn, R Zhou, J Fuk-Woo Chan, ZW Chen

2023-06-01

Background: The SARS-CoV-2 global pandemic has fuelled the generation of vaccines at an unprecedented pace and scale. However, man..

Glycolipids from the gut symbiont Bacteroides fragilis are agonists for natural killer T cells and induce their regulatory differentiation

G Cameron, T Nguyen, M Ciula, SJ Williams, DI Godfrey

2023-05-27

Natural Killer T (NKT) cells are a lipid-antigen reactive T cell subset that is restricted to the antigen presenting molecule CD1d..

Identification of a novel role for the immunomodulator ILRUN in the development of several T cell subsets in mice

L Tribolet, AM Brice, TS Fulford, DS Layton, DI Godfrey, AGD Bean, CR Stewart

2023-05-01

Inflammation and lipid regulator with UBA-like and NBR1-like domains (ILRUN) is a protein-encoding gene associated with innate imm..

Suppression of MR1 by human cytomegalovirus inhibits MAIT cell activation

CL Ashley, BP McSharry, HEG McWilliam, RJ Stanton, CA Fielding, RA Mathias, DP Fairlie, J McCluskey, JA Villadangos, J Rossjohn, A Abendroth, B Slobedman

2023-02-10

Introduction: The antigen presentation molecule MHC class I related protein-1 (MR1) is best characterized by its ability to presen..

Development of virus-like particles with inbuilt immunostimulatory properties as vaccine candidates

S Collett, L Earnest, J Carrera Montoya, MA Edeling, A Yap, CY Wong, D Christiansen, J Roberts, J Mumford, V Lecouturier, V Pavot, S Marco, JK Loi, C Simmons, SA Gulab, JM Mackenzie, A Elbourne, PA Ramsland, G Cameron, D Hans

2023-01-01

The development of virus-like particle (VLP) based vaccines for human papillomavirus, hepatitis B and hepatitis E viruses represen..

Biparatopic nanobodies targeting the receptor binding domain efficiently neutralize SARS-CoV-2

P Pymm, SJ Redmond, O Dolezal, F Mordant, E Lopez, JP Cooney, KC Davidson, ER Haycroft, CW Tan, R Seneviratna, SL Grimley, DFJ Purcell, SJ Kent, AK Wheatley, LF Wang, A Leis, A Glukhova, M Pellegrini, AW Chung, K Subbarao

2022-11-18

The development of therapeutics to prevent or treat COVID-19 remains an area of intense focus. Protein biologics, including monocl..

Fc engineered ACE2-Fc is a potent multifunctional agent targeting SARS-CoV2

BD Wines, L Kurtovic, HM Trist, S Esparon, E Lopez, K Chappin, LJ Chan, FL Mordant, WS Lee, NA Gherardin, SK Patel, GE Hartley, P Pymm, JP Cooney, JG Beeson, DI Godfrey, LM Burrell, MC van Zelm, AK Wheatley, AW Chung

2022-07-28

Joining a function-enhanced Fc-portion of human IgG to the SARS-CoV-2 entry receptor ACE2 produces an antiviral decoy with strain ..

The NKT cell TCR repertoire can accommodate structural modifications to the lipid and orientation of the terminal carbohydrate of iGb3

G Cameron, JMH Cheng, DI Godfrey, MSM Timmer, BL Stocker, EM Dangerfield

2022-06-22

Isoglobotrihexosylceramide (iGb3) is a known NKT cell agonist, however the specific interactions required to trigger NKT cell TCR ..

MAIT and Vδ2 unconventional T cells are supported by a diverse intestinal microbiome and correlate with favorable patient outcome after allogeneic HCT

H Andrlová, O Miltiadous, AI Kousa, A Dai, S DeWolf, S Violante, HY Park, S Janaki-Raman, R Gardner, S El Daker, J Slingerland, P Giardina, A Clurman, ALC Gomes, C Nguyen, MB Da Silva, GK Armijo, N Lee, R Zappasodi, R Chaligne

2022-05-25

Microbial diversity is associated with improved outcomes in recipients of allogeneic hematopoietic cell transplantation (allo-HCT)..

The Efficacy of Common Household Cleaning Agents for SARS-CoV-2 Infection Control

CF Almeida, DFJ Purcell, DI Godfrey, JL McAuley

2022-04-01

The COVID-19 pandemic caused by SARS-CoV-2 is having devastating effects on a global scale. Since common household disinfectants a..

Are NKT cells a useful predictor of COVID-19 severity?

HF Koay, NA Gherardin, THO Nguyen, W Zhang, JR Habel, R Seneviratna, F James, NE Holmes, OC Smibert, CL Gordon, JA Trubiano, K Kedzierska, DI Godfrey

2022-02-08