11 January 2019, Tower Hill, London
Building on the success of the inaugural meeting on B cells in November 2018, the Comparative & Veterinary Immunology Group (CVIG), an Affinity Group of the BSI, organised a second meeting on non-conventional T cells. This topic is of great interest to veterinary immunologists because of the wide variations in numbers of these cells in commercially important animal species.
Adrian Smith chaired the morning session on gd T cells, in which Cynthia Baldwin defined the major subsets, distribution and function of gd T cells in cattle, where these cells are very prominent, emphasising how the ability of gd to migrate to the site of infection and respond early is crucial for protection. Janice Telfer went on to describe bovine WC proteins, which belong to the scavenger cysteine-rich (SRCR) superfamily, and their multifaceted role in the gd T cell response to bacteria, including acting as hybrid pattern recognition receptors and TCR co-receptors. Adrian Smith compared the gd TCR repertoire in mice and birds and discussed the implications of the data for the function of gd T cells in these species. He contrasted mice and humans with small proportions of gd cells with other species with much larger populations of these cells.
Adrian Hayday continued the focus on the gd T cell receptor (TCR). He illustrated the paradoxical nature of gd T cells by demonstrating elegantly that gd TCR combine innate with adaptive immunity by utilizing spatially distinct regions for agonist selection and antigen responsiveness. Ben Wilcox refined the description of human gd T-cells by distinguishing two populations among Vd2+ T-cells, innate-like (Vg9+) and adaptive (Vg9-) subsets, which have distinct functions in microbial immunosurveillance. To round up the session, Andrew McMichael switched gear and talked about the highly conserved non-classical MHC-E class I molecule, which has a role in both NK cell regulation and antigen presentation to CD8+ T cells. The induction of protective pathogen-specific MHC-E-restricted CD8+ T cell responses in rhesus macaques after vaccination with rhesus cytomegalovirus (RhCMV)-based vaccine vectors demonstrates that MHC-E is a new target for novel vaccine and immunotherapeutic modalities. He described how the structure of the TAPBPR -MHCI complex defines the mechanism of peptide loading, editing and binding permissiveness of MHC-E.
The NK cell session was chaired by Dimitra Peppa. NK cells were discussed in the context of bacterial and viral infections in humans and livestock species, notably pigs and cattle. Compelling evidence indicate that these species are appropriate models for human disease. The utility of accessing larger volumes of blood sequentially, tissue availability and surgical interventions in analysing infectious disease models, was elegantly shown by Jayne Hope. In post-BCG vaccinated neonatal calves, NK cells were shown to cluster around dendritic cells and macrophages in lymph nodes draining the site of vaccination. Kerstin Mair described the role of NK cells with the core phenotype CD3-ve, CD8alpha+ve, CD16+ve and perforin +ve in the porcine immune response. In contrast, CD335/ NKp46/ NCR1 expression, IFN-g production and cytolytic capacity were shown to be variable and anatomical site dependent. Dimitra Peppa discussed the role of adaptive NK cells in immune surveillance in human patients with chronic HIV. The importance of RAB11FIP5 differential expression and dysregulation of NK cell activity was explored in HIV patients with broadly neutralising antibodies.
Paul Klenerman chaired the final session on Mucosal Associated Invariant T (MAIT) cells and gave an overview of the MAIT’s and their importance in protection against bacterial and lethal influenza infection. Transcription profiling of MAITs activated through TCR or cytokine stimulation leads to different expression profiles, characterised by tissue repair or pro-inflammatory phenotypes respectively. Olivier Lantz discussed the conservation of MR1 and the recently identified MHC-X across species and that MHC-X and TRAV41 orthologue genes may also have co-evolved. The final speaker of the day was Mariolina Salio, who demonstrated ligand-dependent modulation of MR1-restricted antigen presentation and the identification of a novel small molecule, which prevents MR1 translocation to the cell surface. She showed the role of RibB in MAIT activation. Differential modulation of this pathway by Salmonella strains may lead to increased pathogenicity.
This was a very stimulating and informative meeting, which brought together experts in large farm animals, chickens, mice and humans, providing an excellent opportunity to compare non-conventional T cells across these species. The excellent organisation, stunning setting overlooking Tower Bridge and the Thames, and good food and refreshments, all contributed to the lively discussion and success of the meeting. Feedback was that “this was a great little meeting – there should be more like this”.
The meeting was attended by 100 delegates. We are grateful to the BSI and the UK Veterinary Vaccinology Network (UK VVN) for their support. The UK VVN also sponsored nine ECRs to attend this meeting. Finally, we want to thank the Scientific Sponsors: Biolegend, Fluidigm, Mabtech, MilenyiBiotec and Moredun Scientific, for their presence and support at the meeting.
Programme
Immune surveillance by γδ, MHC-E restricted and iNK cells (part 1). Chair Adrian Smith
09:00 Cynthia Baldwin (University of Massachusetts Amhurst, USA) - Bovine γδ T-cell
09:30 Adrian Smith (University of Oxford, UK) - Avian γδ T-cell
10:00 Adrian Hayday (Francis Crick Institute, UK) - Development and regulation of γδ
Immune surveillance by γδ and MHC-E restricted cells (part 2)
11:00 Ben Wilcox (University of Birmingham, UK) - γδ cells in disease
11:30 Janice Telfer (University of Massachusetts Amhurst, USA) - Bovine γδ T-cells
12:00 Andrew McMichael (University of Oxford, UK) - MHC-E restricted cells
NK cells in health and disease Chair Dimitra Peppa
14:00 Kerstin Mair (University of Veterinary Medicine Vienna, Austria) - Porcine NK cells
14:30 Dimitra Peppa (University of Oxford, UK) - NK cells in HIV
15:00 Jayne Hope (Roslin Institute, UK) - Bovine NK cells in tuberculosis
MAIT cells across species Chair Paul Klenerman
16:00 Paul Klenerman (University of Oxford, UK) - Human and mouse MAITs
16:30 Olivier Lantz (Institut Curie, France) - MAITs cells across species
17:00 Mariolina Salio (University of Oxford, UK) - Ligand-dependent modulation of MR1-restericted antigen presentation