Source: UNIV OF MASSACHUSETTS submitted to NRP
ROLE OF THE T CELL RECEPTOR IN INTERACTING WITH WC1 FOR BOVINE GAMMA DELTA T CELL ACTIVATION
Sponsoring Institution
National Institute of Food and Agriculture
Project Status
COMPLETE
Funding Source
AFRI COMPETITIVE GRANT
Reporting Frequency
Annual
Accession No.
1012377
Grant No.
2017-67015-26631
Cumulative Award Amt.
$460,000.00
Proposal No.
2016-09379
Multistate No.
(N/A)
Project Start Date
Jun 1, 2017
Project End Date
May 31, 2021
Grant Year
2017
Program Code
[A1221]- Animal Health and Production and Animal Products: Animal Health and Disease
Recipient Organization
UNIV OF MASSACHUSETTS
(N/A)
AMHERST,MA 01003
Performing Department
Veterinary & Animal Sciences
Non Technical Summary
Vaccines are the cheapest and most effective medical treatment capable of preventing the negative affects of infections and potentially eradicating infectious diseases. However, currentvaccinestarget only a portionof the infected individual's or animal's aresenal of available immune system responses. (The immune system is what prevents or controls infectious diseases in mammals, including humans and livestock, poultry and fish.) Vaccines to some infectious diseases could be improved byengagingmore than just one aspect of the immune system. The cells we propose to study here, known as gamma deltaT lymphocytes or T cells, have an advantage over those immune system cells targeted bycurrently available vaccinesin that gamma delta T cells canrespond more rapidly after an individual or animal becomes infected. They also are the majority of lymphocytes found in the blood of young cattle, the species of animal with which we do research, suggesting these cells are of particular importance to the survival of the animal.Despite their potential, little is known about the basic biology of how gamma deltaT cells are activated by infectious agents and, thus, little is known about how vaccines could be designed or to recruit them.The knowledge we propose to generate could be used to developnext generation vaccines that engage these gamma deltaT cells so that they can express functions that will help control or prevent infectious disease. To do this we need to understand how the cells identifyinfectious agents, that is,identify the special molecules on their surface that mediate thisinteraction. We will study this using advanced types of microscopy that allow us to evaluate the interaction of individual molecules on the gamma delta T cells with one another and with the infectious agent. We will also evaluate the relative importance of the two principal types of molecules we are studying by evaluating their diversity specifically on gamma delta T cells that areactivated after encountering the bacteria. We will use the bacteriathat cause the diseases known as leptospirosis and tuberculosis. To study the molecules we will use a technique known as high throughput genetic sequencing that can compare millions of different genes expressed. We can also evaluate the interaction of these molecules with the bacteria and assesstheir role in engaging the gamma delta T cells by constructing artificial cells containing these molecules.Designing vaccines that engage gamma delta T cells willenhanceUS agriculture through improvements in animal health thereby contributingto satisfying human food and fiber needs and enhancinganimal well-being. Such vaccines could reduceeconomic losses by farmers occurring as a result of infection intheir livestock. The ability to develop more effective vaccines will also benefit the public by reducing the cost of raising animals for food and thus lower food prices. It could alsohave ancillary benefits by decreasingthe spread ofdiseases from animals to humans (known as zoonotic diseases)and increasing public confidence in the food supply.
Animal Health Component
20%
Research Effort Categories
Basic
80%
Applied
20%
Developmental
0%
Classification

Knowledge Area (KA)Subject of Investigation (SOI)Field of Science (FOS)Percent
31134101090100%
Knowledge Area
311 - Animal Diseases;

Subject Of Investigation
3410 - Dairy cattle, live animal;

Field Of Science
1090 - Immunology;
Goals / Objectives
Our over-arching hypothesis is to improve food animal health through targeting of the immune system in an appropriate manner.Our long-term goal with regard to the research in this projectis to define recognition structures used bygamma delta T lymphocytes (or T cells) to interactwith infectious disease agents or microbial pathogens so that these broadly-reactive T cells may be targeted in next generation vaccines or therapeutics requiring activation of specific components of the immune response.Since gamma delta T cells make up to more than half of mononuclear cells in bloodin young ruminants and pigs, it is logical to define mechanisms by which they may be activated in a targeted manner.WC1 proteins are a family of molecules uniquely expressed by gamma delta T cells in ruminants and swine as well as other food animal species. They act aspattern recognition receptors (PRR), meaning they bind specifically to pathogens,as well asacting as co-receptors meaning they alert the T cell when a pathogen has been encountered/bound thereby contributing to the activation of that cell. An activated cell displays functionsconsistent with protective immunity.Since cells cannot be activated through WC1 alone, our hypothesis is that WC1 molecules actas PRR and activating receptors for WC1+ gamma delta T cells in conjunction with theT cell receptor (TCR) but that they may be the determing factor in cell response to pathogens. Because WC1 is a multigeneic array there are more than 130possible microbe-binding domains.Once we have a more complete understanding of how a gamma delta T cell is activated we may devise methods to target these cells for engagement artificially in vaccine constructs. The specific objectives are:1. Evaluate the direct physical interactions among WC1 co-receptors and the TCR. If these two molecules are acting in concert it should be possible to observe direct interactions in microbe-activated cells.2. Determine the gamma deltaTCR mRNAtranscript sequences of pathogen-responsive and nonresponsive gamma deltaT cells that have identical WC1 gene expression to examine their TCRsfor polyclonal, oligoclonal or monoclonal nature.3. Use a WC1-gamma deltaTCR reconstitution system to directly test the role of WC1 molecules and TCR chains in gamma deltaT cell responses to pathogens.This proposal deals with "disease prevention" including "vaccine development and enhancing innate and/or adaptive immunity" since gamma delta T cells form a bridge between innate and adaptive immunity. Once activation of gamma delta T cells is fully understood they could be used for "therapeutic interventions for disease reduction/treatment" as for cancer therapy. It is also feasible that this approach could be adopted in cattle to target infectious diseases.
Project Methods
Methods:Objective 1. Evaluate the direct physical interactions among bovine WC1 co-receptors and the T cell receptor (TCR). Using fluorescence resonance energy transfer (FRET) and immunoprecipitation we will evaluate the physical association of WC1s with TCRs when gamma delta T cells are activated by a pathogen, since this has not been formally established. We expect to find both receptors clustered in the immune synapse, whether WC1 and TCR are co-ligated or TCR alone is ligated and transmits the signal. In addition, using ImageStream technology (a combination of flow cytometry with brightfield, darkfield and fluorescent images), we will determine if two populations of Leptospira-binding cells can be distinguished: one population would consist of cells in which WC1 and TCR co-localize and also form an association close enough to transfer energy by FRET due to co-ligation by the pathogen, while a second population would consist of cells in which TCR and WC1 are found in the immunological synapse but do not form a "close association" as known to occur for alpha betaT cells. If so, these two populations can be sorted by the ImageStream and their TCR sequences examined in Objective 2. We also expect to be able to use a new technology known as dSTORM, a type of microscopy that images single molecules, to evaluate the relationship of TCR and WC1 molecules in resting and activated gamma delta T cells.Objective 2. Determine the gammadelta T cell receptor transcript sequences of pathogen-responsive and nonresponsive bovinegamma delta T cells that have identical WC1 gene expression to examine them for polyclonal, oligoclonal or monoclonal nature. We have observed that only some members of the subpopulation of bovinegammadelta T cells known as WC1.3+ respond to Leptospira, yet cells within this subset only express twoWC1 genes: WC1-3 and WC1-8. We expect those that respond to Leptospira to have a more restricted repertoire of TCR sequences than the polyclonal repertoire of those that do not. This will yield correlative data regarding the question of whether the TCR of responsive cells is restricted relative to control populations (ex vivo, naïve or non-antigen responsive), suggesting or refuting the antigen specificity of the TCR. Also, if two types of responsive cells are detected in Objective 1 in a larger Leptospira-responsive WC1+ gamma delta T cell population, based on their relative association of TCR with WC1, they will be sorted and analyzed here. Our approach will be to use a unique Next Generation Sequencing (NGS) method to evaluate the transcripts from the responsive and nonresponsive cells in this WC1-defined population.Dr. Connelley at the Roslin Institute is developing a unique protocol to evaluate bovine TCR gene usage that allows tagging of each mRNA transcript so as to eliminate overrepresentation of particular sequences due to PCR bias during amplification steps.Objective 3. Use a WC1-gammadeltaTCR reconstitution system to directly test the role of WC1 molecules and TCR chains in gammadelta T cell responses to pathogens. A TCR-negative human T cell hybridoma cell liine will be used for transduction and expression of various bovine WC1 molecules and TCR chains to determine the components necessary for a response to the pathogens Leptospira and Mycobacteria. Mutations as well as chimeric molecules will be employed to examine the components necessary, including WC1, the TCR complementarity determining regions and the constant domain of the TCR molecule known as C gamma 5. This is a unique system that will allow manipulations including point mutations of the bovine gamma delta T cell receptors and WC1 molecules to assess their relative roles in pathogen responses and cell activation.Efforts: Scientific knowledge will be disseminated by presentations at scientific conferences and workships including local, regional, national and international as well as laboratory instruction and practicum experiences for all levels of learners. Evaluation of success will be defined by accomplishment of oral and poster presentations that demonstate an understanding of the research and an advancement of knowledge as stated in the project objectives as well as acceptance of peer-reviewed publications. Graduate students and post-doctoral fellows will develop a prospectus with timelines as it relates to establishment of procedures and evaluation of result to accomplish the objectives and experiments outlined in the project narrative. It will also be evaluated by the accesibility of data generated from the project including gene transcript sequences and the uptake of the procedures developed during the implementation ofthis project by other scientists working in a related animal health field.

Progress 06/01/17 to 05/31/21

Outputs
Target Audience:Academic peers and vaccine developers in animal health industry. Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided?The project provided training to students at the B.S. level in pre-veterinary science and animal science; training for MS and PhD graduate students and for post-doctoral fellows. How have the results been disseminated to communities of interest?Through peer-reviewed publications of primary results and reviews and at scientific conferences. What do you plan to do during the next reporting period to accomplish the goals? Nothing Reported

Impacts
What was accomplished under these goals? Objective 1 was to evaluate the physical interactions between WC1 and the gamma delta T cell receptor and this was accomplished and has been published in a peer-reviewed publication in Frontiers in Immunology, 2021 Gillespie et al. The results show that these two receptors come together following activation in protein islands that are close enough to result in FRET. Objective 2 was to evaluate the expression of WC1 co-receptor variants by cells that can and those that do not respond to Leptospira following vaccination of cattle and some of these results are found in another publication in Frontiers in Immunology 2019 Damani-Yokota et al. that showed that 80% of cells within the WC1.1+ population of gamma delta T cells that can respond to Leptospira express a WC1 variant that can bind the bacteria. However, the results of the remainder of this objective to evaluate the TCR gene expression is still in preparation for publication although the expreiments have been concluded. The third objective was accomplished in a manner deviant for the initial proposed approach but can be found in a publication that is in press in DCI by Lepage et al. It showed that while the majority of WC1+ gamma delta T cells in cattle, goats and swine do use a specific TCR gamma constant region there are some swine WC1+ gamma delta T cells that do not. Thus, while the use of this constant region seems to be preferred and thus advantageous it is not absolutely required for WC1+ gamma delta T cells to be activated.

Publications

  • Type: Journal Articles Status: Published Year Published: 2021 Citation: 1. Gillespie, A., A. Yirsaw, S. Kim, K. Wilson, J. McLaughlin, M. Madigan, K. Loonie, E. Britton, F. Zhang, P. Damani-Yokota, K.P. Gunasekaran, J. Telfer, and C.L. Baldwin. 2021. Gene characterization and expression of the ?? T cell co-receptor WC1 in sheep. Developmental and Comparative Immunology 116:103911.
  • Type: Journal Articles Status: Published Year Published: 2021 Citation: 2. Yirsaw, A.W., A. Gillespie, E. Britton, A. Doerle, L. Johnson, S. Marston, J. Telfer and C.L. Baldwin. 2021. Goat ?? T cell subpopulations defined by WC1 expression, responses to pathogens and cytokine production. Developmental and Comparative Immunology 118:103984.
  • Type: Journal Articles Status: Published Year Published: 2021 Citation: Baldwin, C.L. Damani-Yokota P, Yirsaw A, Loonie K, Teixeira AF, Gillespie A. 2021. Non Rodent Vertebrate Immunological Research Enlightens the Immune Landscape  Special features of ?? T cells in ruminants. Molecular Immunology 134:161-169.
  • Type: Journal Articles Status: Awaiting Publication Year Published: 2022 Citation: Loonie, K., A.E. Gillespie and C.L. Baldwin. The WC1 ?? T cell pathogen receptor of ruminants is preserved in the genome of ancient extinct Auroch. Immunogenetics, in press.
  • Type: Journal Articles Status: Submitted Year Published: 2022 Citation: Gillespie, A., M.G. Gervasi, J.C. Telfer and C.L. Baldwin. ?? TCR and the WC1 co?receptor interactions in response to Leptospira using imaging flow cytometry and STORM. Frontiers in Immunology, Jul 28;12:712123.
  • Type: Journal Articles Status: Awaiting Publication Year Published: 2022 Citation: LePage, L., A. Gillespie, A. Schlerka, J. Schwartz, C.P. Farrell, E. Lagumdzic, J. Hammond, C. Baldwin, J. Telfer, S.E. Hammer. 2021. Subpopulations of swine ?? T cells defined by TCR? and WC1 gene expression. Developmental and Comparative Immunology, in press.
  • Type: Journal Articles Status: Published Year Published: 2021 Citation: 3. Gillespie, A.E., A. Yirsaw, K.P. Gunasekaran, T.P. Smith, D.M. Bickhart, M. Turley, T. Connelley, J.C. Telfer and C.L. Baldwin. 2021. Characterization of the domestic goat ?? T cell receptor gene loci and gene usage. Immunogenetics 73:187-201.


Progress 06/01/19 to 05/31/20

Outputs
Target Audience:Academic peers and vaccine developers in animal health and pharmaceutical companies. Changes/Problems:None to report except for the interruptions caused as a result of the Covid 19 pandemic that kept some personnel from entering the lab for a period of months. What opportunities for training and professional development has the project provided?Undergraduate students were trained through this grant funding in immunology and animal health and are now in veterinary college. One post-doctoral fellow was trained and 2 PhD students. How have the results been disseminated to communities of interest?Presentations at scientific conferences and through peer-reviewed publications. What do you plan to do during the next reporting period to accomplish the goals?Work on completing the objectives and publishing the results in peer-reviewed journals.

Impacts
What was accomplished under these goals? The WC1 cell surface family of molecules function as hybrid gdTCR co-receptors, augmenting cellular responses when cross-linked with the TCR, and as pattern recognition receptors, binding pathogens. It is known that following activation, key tyrosines are phosphorylated in the intracytoplasmic domains of WC1 molecules and that the cells fail to respond when WC1 is knocked down or, as shown here, when physically separated from the TCR. Based on these results we hypothesized that the colocalization of WC1 and TCR will occur following cellular activation thereby allowing signaling to ensue. We evaluated the spatio-temporal dynamics of their interaction using imaging flow cytometry and stochastic optical reconstruction microscopy. We found that in quiescent gd T cells both WC1 and TCR existed in separate and spatially stable protein domains (protein islands) but after activation using Leptospira, our model system, that they concatenated. The association between WC1 and TCR was close enough for fluorescence resonance energy transfer. Prior to concatenating with the WC1 co-receptor, γ?? T cells had clustering of TCR-CD3 complexes and exclusion of CD45. gd T cells may individually express more than one variant of the WC1 family of molecules and we found that individual WC1 variants are clustered in separate protein islands in quiescent cells. However, the islands containing different variants merged following cell activation and before merging with the TCR islands. While WC1 was previously shown to bind Leptospira in solution, here we showed that Leptospira bound WC1 proteins on the surface of gd T cells and that this could be blocked by anti-WC1 antibodies. In conclusion, gdTCR, WC1 and Leptospira interact directly on the gd T cell surface, further supporting the role of WC1 in γ?? T cell pathogen recognition and cellular activation. This was one of three main objectives for this project.

Publications

  • Type: Journal Articles Status: Published Year Published: 2020 Citation: 1. Baldwin, C.L., A. Yirsaw, A. Gillespie, L. LePage, F. Zhang, P. Damani-Yokota, and J.C. Telfer. 2020. ?? T cells in livestock: Responses to pathogens and vaccine potential. Transboundary and Emerging Diseases 67(Suppl) 2:119-1128.
  • Type: Journal Articles Status: Published Year Published: 2020 Citation: 2. Yirsaw, A., C.L. Baldwin. 2020. Goat ?? T cells. Developmental and Comparative Immunology 114:103809
  • Type: Conference Papers and Presentations Status: Other Year Published: 2019 Citation: Yirsaw, A.* and C.L. Baldwin. Characterization of goat ?? T cells and responses of WC1+ ?? T cells to pathogens. (talk) International Veterinary Immunology Symposium, Seattle, WA Aug 2019.
  • Type: Conference Papers and Presentations Status: Other Year Published: 2019 Citation: Baldwin, C.L. and S. Hammers*. Swine ?? T cell subpopulations defined by WC1 and TCR gene expression. (talk) International Veterinary Immunology Symposium, Seattle, WA Aug 2019.
  • Type: Conference Papers and Presentations Status: Other Year Published: 2019 Citation: Yirsaw, A.* and Baldwin, CL. Characterization of goat ?? T cells and responses of WC1+ ?? T cells to pathogens. (talk) CRWAD, Chicago, IL Dec 2019.
  • Type: Conference Papers and Presentations Status: Other Year Published: 2019 Citation: 6. Gillespie, A.*, M. G. Gervasi, A. Yirsaw, L. LePage, T. Connelley, J. Hope, J.C. Telfer and C.L. Baldwin. " Immune synapse formation of WC1+ ???? T cells in response to Leptospira." (talk) CRWAD, Chicago, IL, Dec 2019.


Progress 06/01/18 to 05/31/19

Outputs
Target Audience:The primary target audiences include academic peers and vaccine developers in animal health and pharmaceutical companies. Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided?Three new undergraduate pre-veterinary students have joined the laboratory and learned both molecular and cellular biology techniques including bioinformatics to analyze PacBio sequences of WC1 genes expressed, flow cytometry and tissue culture. A PhD student has learned mentorship by overseeing these students. One PhD student graduated and has now taken up a post-doctoral fellowship at NY University. One PhD student from University of Massachusetts Amherstreceived traning by working at the Roslin Institute in Edinburgh under co-PIs Connelley and Hope with the direct supervision of a post-doctoral fellow. One US-based PI also visited Roslin Institute to meet with two coPIs and the Roslin Institutes bioinformatics team to discuss adapting the systems for analysis of genes in cattle.Three PI's and a PhD student attended the International Veterinary Vaccinology Network conference in London, UK in January 2019 where they were able to interact with industry vaccinologists, non-profit groups who sponsor vaccinology research and scientists from throughout the world who work in this discipline; here 2 posters of the work of the PI's was presented. Two PI's gave presentations at a Workshop sponsored by the British Society of Immunology to train scientists in understanding Non-conventional T cells in Health and Disease in London in January 2019. One PI also attended the Gamma Delta T cell Symposium in Bordeaux, France in June 2018and presented the team's work and chaired the Opening Session. Here researchers mainly interested in mouse and human gamma delta T cell biology learned about the ruminant system and were interested in our research. How have the results been disseminated to communities of interest? Nothing Reported What do you plan to do during the next reporting period to accomplish the goals?At Roslin Institute cattle are being evaluated for their gamma delta T cells responses to leptospira, Mycobacteria bovis and Theileria annulata. We are determiningthe gamma deltaTCR mRNAtranscript sequences of both pathogen-responsive and nonresponsive gamma deltaT cells (using the SMART system and high throughput sequencing)that have identical WC1 gene expression to examine their TCRsfor polyclonal, oligoclonal or monoclonal nature. Similar evaluations will be conducted at University of Massachusetts. We are usinga WC1-gamma deltaTCR reconstitution system to directly test the role of WC1 molecules and TCR chains in gamma deltaT cell responses to pathogens - this work is ongoing.

Impacts
What was accomplished under these goals? As stated in the previous report, we were able to visualize Leptospira bacteria directly binding to the gamma delta T cells and co-localizing with WC1 molecules on their surface using STORM, which is a very high resolution microscopy. The constructs needed to evaluate the role of the various T cell receptor domains (constant and variable regions) have been made from cloned gamma delta T cells from vaccinated cattle andthat react with Leptospira in recall responses in vitro. The constant and variable domains of the TCR gamma chain have been substituted by PCR using an overlapping strategy. Transfection protocols have been optimized and 293t cells shown to express WC1 transfected genes. These will be combined with TCR gene expression as well. Next generation sequencing protocols using the SMART system have now been optimized to evaluate TCR gamma and delta gene expressioin by bacterial and protozoal responsive and nonresponsive cells as well as the WC1 genes expressed. This system allows quantification of transcripts with particular sequences. Working with bioinformaticians at Roslin Institute glitches in data analysis have been identified and modified.

Publications

  • Type: Journal Articles Status: Published Year Published: 2018 Citation: Bovine T cell receptors and ?? WC1 co-receptor transcriptome analysis during the first month of life. Damani-Yokota P, Gillespie A, Pasman Y, Merico D, Connelley TK, Kaushik A, Baldwin CL. Dev Comp Immunol. 2018 Nov;88:190-199. doi: 10.1016/j.dci.2018.07.023. Epub 2018 Jul 23.
  • Type: Journal Articles Status: Published Year Published: 2018 Citation: Variegated Transcription of the WC1 Hybrid PRR/Co-Receptor Genes by Individual ?? T Cells and Correlation With Pathogen Responsiveness. Damani-Yokota P, Telfer JC, Baldwin CL. Frontiers in Immunology 9:717.


Progress 06/01/17 to 05/31/18

Outputs
Target Audience:The primary target auidences include academic peers and vaccine developers in animal health and pharmaceutical companies Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided?A graduate student and a post-doctoral fellow were able to work together to develop the 2-color STORM analysis; this was the first use of this highly sophisticated microscopyon campus. Undergraduate honors students have been involved with the analysis of expressed T cell receptor genes and WC1 genes, developing protocol for generating and analyzing high throughput sequencing of long reads using PacBio; the preparation of material and analysis were done at UMass Amherst while the physical sequencing was donein conjunction with University of Massachusetts Medical School's core facility. Two pre-veterinary honors students were able to present their work at the Massachusetts Undergraduate Research Symposium as well as participate in a course on oral presentation. How have the results been disseminated to communities of interest?Presentations at national and international scientific conferences: Gillespie A., Connelley T., Telfer J.C., Baldwin C.L. "Interaction of γδ TCR with the WC1 hybrid coreceptor/pathogen recognition receptor in cattle" (poster) American Association of Immunologists (AAI) meeting. Washington, D.C., USA. May 12-16, 2017. Baldwin, CL and Telfer, JC. Keynote address on WC1 and the role of these molecules in gamma delta T cell activationat the Immunology Symposium, associated with CRWAD, Chicago, IL, Dec 2017. What do you plan to do during the next reporting period to accomplish the goals?We are continuing to refine the method to visualize Leptospira binding directly to gamma delta T cells using Amnis and STORM. While it is possible to do this because of the large size of the bacteria some modification will be necessary to quantitate the direct interaction of the bacteria with specific cell membrane molecules of the lymphocytes. Experiment to address Objective 3 will be carried out once the cells have been transfected with both the TCR constructs and the WC1 molecules.

Impacts
What was accomplished under these goals? Objective 1: using imaging flow cytometry (Amnis) we have been able to show direct interaction of the TCR and WC1 following activation of the cells with Leptospira organisms and plot a time course. These molecules (TCR and WC1) have shown fluorescence resonance energy transfer (FRET) following activation indicating that they are within 9 nm. Using Stochastic Optimal Reconstruction Microscopy (STORM) we have been able to pinpoint the interaction of individual molecules. STORM is considerably more resolute than for example confocal microscopy. Objective 2: This is ongoing and no conclusive results are reported that allow us to address the hypothesis. However using gamma delta T cell clones we have determined that the expression of WC1 genes (of which there are 13) is more complex than previous data suggested. This has been published. Objective 3: A TCR has been cloned from a leptospira-responsive cell and the gamma and delta chains cloned and sequenced.The constructs have been made which swap outTCR constant genes or variable genes for those from non-leptoresponsive cells which will be used to address the objective. Transfection of cells with a construct of WC1 has been achieved and currently the protocol is being optimized to increase efficiency to gain a high proportion of transfected cells.

Publications

  • Type: Journal Articles Status: Published Year Published: 2018 Citation: Variegated transcription of the WC1 hybrid PRR/co-receptor genes by individual gamma delta T cells and correlation with pathogen responsiveness. P. Damani-Yokota, J. C. Telfer, and C,.L. Baldwin.
  • Type: Journal Articles Status: Under Review Year Published: 2018 Citation: Bovine T cell receptors and gamma delta WC1 co-receptor transcriptome analysis during the first month of life. P. Damani-Yokota, A. Gillespie, Y Pasman, D. Merico, T.K. Connelley, A. Kaurshik and C.L. Baldwin, Developmental and Comparative Immunology, under revision.
  • Type: Journal Articles Status: Published Year Published: 2017 Citation: PrabhuDas MR, C.L. Baldwin, P.L. Bollyky, D.M.E. Bowdish, K. Drickamer, M. Febbraio, J. Herz, L. Kobzik, M. Krieger, J. Loike, B. McVicker, T.K. Means, S.K. Moestrup, S.R. Post, T. Sawamura, S. Silverstein, R.C. Speth, J.C. Telfer, G.M. Thiele, X.Y. Wang, S.D. Wright, J. El Khoury. 2017. A consensus definitive classification of scavenger receptors and their roles in health and disease. J Immunol. 198:3775-3789.