scholarly journals A transplantable tumor model allowing investigation of NY-BR-1-specific T cell responses in HLA-DRB1*0401 transgenic mice

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Krishna Das ◽  
David Eisel ◽  
Mathias Vormehr ◽  
Karin Müller-Decker ◽  
Adriane Hommertgen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
T Cell ◽  
Cell Line ◽  
In Silico ◽  
Cell Epitope ◽  
Tumor Model ◽  
T Cell Responses ◽  
T Cell Epitope ◽  
Cell Responses

Abstract Background NY-BR-1 has been described as a breast cancer associated differentiation antigen with intrinsic immunogenicity giving rise to endogenous T and B cell responses. The current study presents the first murine tumor model allowing functional investigation of NY-BR-1-specific immune responses in vivo. Methods A NY-BR-1 expressing tumor model was established in DR4tg mice based on heterotopic transplantation of stable transfectant clones derived from the murine H2 compatible breast cancer cell line EO771. Composition and phenotype of tumor infiltrating immune cells were analyzed by qPCR and FACS. MHC I binding affinity of candidate CTL epitopes predicted in silico was determined by FACS using the mutant cell line RMA-S. Frequencies of NY-BR-1 specific CTLs among splenocytes of immunized mice were quantified by FACS with an epitope loaded Db-dextramer. Functional CTL activity was determined by IFNγ catch or IFNγ ELISpot assays and statistical analysis was done applying the Mann Whitney test. Tumor protection experiments were performed by immunization of DR4tg mice with replication deficient recombinant adenovirus followed by s.c. challenge with NY-BR-1 expressing breast cancer cells. Results Our results show spontaneous accumulation of CD8+ T cells and F4/80+ myeloid cells preferentially in NY-BR-1 expressing tumors. Upon NY-BR-1-specific immunization experiments combined with in silico prediction and in vitro binding assays, the first NY-BR-1-specific H2-Db-restricted T cell epitope could be identified. Consequently, flow cytometric analysis with fluorochrome conjugated multimers showed enhanced frequencies of CD8+ T cells specific for the newly identified epitope in spleens of immunized mice. Moreover, immunization with Ad.NY-BR-1 resulted in partial protection against outgrowth of NY-BR-1 expressing tumors and promoted intratumoral accumulation of macrophages. Conclusion This study introduces the first H2-Db-resctricted CD8+ T cell epitope-specific for the human breast cancer associated tumor antigen NY-BR-1. Our novel, partially humanized tumor model enables investigation of the interplay between HLA-DR4-restricted T cell responses and CTLs within their joint attack of NY-BR-1 expressing tumors.

scholarly journals Breadth of CD8 T-cell mediated inhibition of replication of diverse HIV-1 transmitted-founder isolates correlates with the breadth of recognition within a comprehensive HIV-1 Gag, Nef, Env and Pol potential T-cell epitope (PTE) peptide set

PLoS ONE ◽  
2021 ◽  
Vol 16 (11) ◽  
pp. e0260118
Author(s):  
Peter Hayes ◽  
Natalia Fernandez ◽  
Christina Ochsenbauer ◽  
Jama Dalel ◽  
Jonathan Hare ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Cell Epitope ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
T Cell Epitope ◽  
Cell Numbers ◽  
Cell Responses ◽  
Hiv 1

Full characterisation of functional HIV-1-specific T-cell responses, including identification of recognised epitopes linked with functional antiviral responses, would aid development of effective vaccines but is hampered by HIV-1 sequence diversity. Typical approaches to identify T-cell epitopes utilising extensive peptide sets require subjects’ cell numbers that exceed feasible sample volumes. To address this, CD8 T-cells were polyclonally expanded from PBMC from 13 anti-retroviral naïve subjects living with HIV using CD3/CD4 bi-specific antibody. Assessment of recognition of individual peptides within a set of 1408 HIV-1 Gag, Nef, Pol and Env potential T-cell epitope peptides was achieved by sequential IFNγ ELISpot assays using peptides pooled in 3-D matrices followed by confirmation with single peptides. A Renilla reniformis luciferase viral inhibition assay assessed CD8 T-cell-mediated inhibition of replication of a cross-clade panel of 10 HIV-1 isolates, including 9 transmitted-founder isolates. Polyclonal expansion from one frozen PBMC vial provided sufficient CD8 T-cells for both ELISpot steps in 12 of 13 subjects. A median of 33 peptides in 16 epitope regions were recognised including peptides located in previously characterised HIV-1 epitope-rich regions. There was no significant difference between ELISpot magnitudes for in vitro expanded CD8 T-cells and CD8 T-cells directly isolated from PBMCs. CD8 T-cells from all subjects inhibited a median of 7 HIV-1 isolates (range 4 to 10). The breadth of CD8 T-cell mediated HIV-1 inhibition was significantly positively correlated with CD8 T-cell breadth of peptide recognition. Polyclonal CD8 T-cell expansion allowed identification of HIV-1 isolates inhibited and peptides recognised within a large peptide set spanning the major HIV-1 proteins. This approach overcomes limitations associated with obtaining sufficient cell numbers to fully characterise HIV-1-specific CD8 T-cell responses by different functional readouts within the context of extreme HIV-1 diversity. Such an approach will have useful applications in clinical development for HIV-1 and other diseases.

scholarly journals Specificity of CD8+ T-Cell Responses Following Vaccination with Conserved Regions of HIV-1 in Nairobi, Kenya

Vaccines ◽  
2020 ◽  
Vol 8 (2) ◽  
pp. 260
Author(s):  
Yehia S. Mohamed ◽  
Nicola J. Borthwick ◽  
Nathifa Moyo ◽  
Hayato Murakoshi ◽  
Tomohiro Akahoshi ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Lines ◽  
Cd8 T Cells ◽  
Cell Epitope ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
T Cell Epitope ◽  
Cell Responses ◽  
Hiv 1

Sub-Saharan Africa carries the biggest burden of the human immunodeficiency virus type 1 (HIV-1)/AIDS epidemic and is in an urgent need of an effective vaccine. CD8+ T cells are an important component of the host immune response to HIV-1 and may need to be harnessed if a vaccine is to be effective. CD8+ T cells recognize human leukocyte antigen (HLA)-associated viral epitopes and the HLA alleles vary significantly among different ethnic groups. It follows that definition of HIV-1-derived peptides recognized by CD8+ T cells in the geographically relevant regions will critically guide vaccine development. Here, we study fine details of CD8+ T-cell responses elicited in HIV-1/2-uninfected individuals in Nairobi, Kenya, who received a candidate vaccine delivering conserved regions of HIV-1 proteins called HIVconsv. Using 10-day cell lines established by in vitro peptide restimulation of cryopreserved PBMC and stably HLA-transfected 721.221/C1R cell lines, we confirm experimentally many already defined epitopes, for a number of epitopes we define the restricting HLA molecule(s) and describe four novel HLA-epitope pairs. We also identify specific dominance patterns, a promiscuous T-cell epitope and a rescue of suboptimal T-cell epitope induction in vivo by its functional variant, which all together inform vaccine design.

scholarly journals The Human CD4+ T Cell Response against Mumps Virus Targets a Broadly Recognized Nucleoprotein Epitope

2019 ◽  
Vol 93 (6) ◽  
Author(s):  
Jelle de Wit ◽  
Maarten E. Emmelot ◽  
Martien C. M. Poelen ◽  
Josien Lanfermeijer ◽  
Wanda G. H. Han ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Clone ◽  
Cell Epitope ◽  
T Cell Responses ◽  
Mumps Virus ◽  
T Cell Epitope ◽  
Cell Responses ◽  
Hla Dr ◽  
T Cell Clone

ABSTRACT Mumps outbreaks among vaccinated young adults stress the need for a better understanding of mumps virus (MuV)-induced immunity. Antibody responses to MuV are well characterized, but studies on T cell responses are limited. We recently isolated a MuV-specific CD4+ T cell clone by stimulating peripheral blood mononuclear cells (PBMCs) from a mumps case with the viral nucleoprotein (MuV-N). In this study, we further explored the identity and relevance of the epitope recognized by the CD4+ T cell clone and ex vivo by T cells in a cohort of mumps cases. Using a two-dimensional matrix peptide pool of 15-mer peptides covering the complete MuV-N, we identified the epitope recognized by the T cell clone as MuV-N110–124 GTYRLIPNARANLTA, present in a well-conserved region of the viral protein. Upon peptide-specific stimulation, the T cell clone expressed the activation marker CD137 and produced gamma interferon, tumor necrosis factor, and interleukin-10 in a HLA-DR4-restricted manner. Moreover, the CD4+ T cells exerted a cytotoxic phenotype and specifically killed cells presenting MuV-N110–124. Furthermore, the identified peptide is widely applicable to the general population since it is predicted to bind various common HLA-DR molecules, and epitope-specific CD4+ T cells displaying cytotoxic/Th1-type properties were found in all tested mumps cases expressing different HLA-DR alleles. This first broadly recognized human MuV-specific CD4+ T cell epitope could provide a useful tool to detect and evaluate virus-specific T cell responses upon MuV infection or following vaccination. IMPORTANCE Recent outbreaks of mumps among vaccinated young adults have been reported worldwide. Humoral responses against mumps virus (MuV) are well characterized, although no correlate of protection has been elucidated, stressing the need to better understand cellular MuV-specific immunity. In this study, we identified the first MuV T cell epitope, which is derived from the viral nucleoprotein (MuV-N) and was recognized by a cytotoxic/Th1 CD4+ T cell clone that was isolated from a mumps case. Moreover, the epitope was predicted to bind a broad variety of common HLA-DRB1 alleles, which was confirmed by the epitope-specific cytotoxic/Th1 CD4+ T cell responses observed in multiple mumps cases with various HLA-DRB1 genotypes. The identified epitope is completely conserved among various mumps strains. These findings qualify this promiscuous MuV T cell epitope as a useful tool for further in-depth exploration of MuV-specific T cell immunity after natural mumps virus infection or induced by vaccination.

scholarly journals 248 Empiric profiling of peripheral T cell recall responses to tumor mutanomes versus in silico predictions in NSCLC patients undergoing pembrolizumab treatment ± chemotherapy

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A268-A268
Author(s):  
Madison Milaszewski ◽  
James Loizeaux ◽  
Emily Tjon ◽  
Crystal Cabral ◽  
Tulin Dadali ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Combination Therapy ◽  
In Silico ◽  
Ex Vivo ◽  
T Cell Responses ◽  
Patient Specific ◽  
In Silico Prediction ◽  
Cell Responses ◽  
In Silico Predictions

BackgroundEffective immune checkpoint blockade (ICB) treatment is dependent on T-cell recognition of patient-specific mutations (neoantigens). Empirical identification of neoantigens ex vivo has revealed shortcomings of in silico predictions.1 To better understand the impact of ICB treatment on T cell responses and differences between in silico and in vitro methods, neoantigen-specific T cell responses were evaluated in patients with non-small cell lung cancer undergoing first-line therapy with pembrolizumab ± chemotherapy.MethodsTumor and whole blood samples were collected from 14 patients prior to and after immunotherapy; seven each in monotherapy and combination therapy cohorts. The ex vivo ATLAS™ platform was used to profile neoantigen-specific T-cell responses. Patient-specific tumor mutations identified by next-generation sequencing (NGS) were expressed individually as ATLAS clones, processed patient-specific autologous antigen presenting cells, and presented to their T cells in vitro. ATLAS-verified antigens were compared with epitope predictions made using algorithms.ResultsOn average, 150 (range 37–339) non-synonymous mutations were identified. Pre-treatment, ATLAS identified T cell responses to a median of 15% (9–25%) of mutations, with nearly equal proportions of neoantigens (8%, 5–15%) and Inhibigens™, targets of suppressive T cell responses (8%, 3–13%). The combination therapy cohort had more confirmed neoantigens (46, 20–103) than the monotherapy cohort (7, 6–79). After treatment, the median ratio of CD4:CD8 T cells doubled in the monotherapy but not combination cohort (1.2 to 2.4 v. 1.6 to 1.3). Upon non-specific stimulation, T cells from patients on combination therapy expanded poorly relative to monotherapy (24 v. 65-fold, p = 0.014); no significant differences were observed pre-treatment (22 v. 18-fold, p = 0.1578). Post-treatment, the median number of CD8 neoantigens increased in the combination therapy cohort (11 to 15) but in monotherapy were mostly unchanged (6 to 7). Across timepoints, 36% of ATLAS-identified responses overlapped. In silico analysis resulted in 1,895 predicted epitopes among 961 total mutations; among those, 30% were confirmed with ATLAS, although nearly half were Inhibigens, which could not be predicted. Moreover, 50% of confirmed neoantigens were missed by in silico prediction.ConclusionsMonotherapy and combination therapy had differential effects on CD4:CD8 T cell ratios and their non-specific expansion. A greater proportion of neoantigens was identified than previously reported in studies employing in silico predictions prior to empirical verification.2 Overlap between confirmed antigens and in silico prediction was observed, but in silico prediction continued to have a large false negative rate and could not characterize Inhibigens.AcknowledgementsWe would like to acknowledge and thank the patients and their families for participating in this study.ReferencesLam H, McNeil LK, Starobinets H, DeVault VL, Cohen RB, Twardowski P, Johnson ML, Gillison ML, Stein MN, Vaishampayan UN, DeCillis AP, Foti JJ, Vemulapalli V, Tjon E, Ferber K, DeOliveira DB, Broom W, Agnihotri P, Jaffee EM, Wong KK, Drake CG, Carroll PM, Davis TA, Flechtner JB. An empirical antigen selection method identifies neoantigens that either elicit broad antitumor T-cell responses or drive tumor growth. Cancer Discov 2021;11(3):696–713. doi: 10.1158/2159- 8290.CD-20-0377. Epub 2021 January 27. PMID: 33504579. Rosenberg SA. Immersion in the search for effective cancer immunotherapies. Mol Med 27,63(2021). https://doi.org/10.1186/s10020-021-00321-3

scholarly journals 65 Identification of frequently presented non-mutated tumor-specific immunogens for the development of both off-the-shelf and personalized vaccines without need for tumor biopsy

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A72-A72
Author(s):  
Orsolya Lorincz ◽  
Levente Molnar ◽  
Zsolt Csiszovszki ◽  
Eszter Somogyi ◽  
Jozsef Toth ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Colorectal Cancer ◽  
T Cells ◽  
T Cell ◽  
Metastatic Colorectal Cancer ◽  
Cancer Vaccines ◽  
T Cell Responses ◽  
Tumor Biopsy ◽  
Cell Responses ◽  
Antigen Selection

BackgroundVaccines have little chance of destroying heterogeneous tumor cells since they rarely induce polyclonal T-cell responses against the tumor. The main challenge is the accurate identification of tumor targets recognizable by T cells. Presently, 6–8% of neoepitopes selected based on the patients‘ tumor biopsies are confirmed as real T cell targets.1 2. To overcome this limitation, we developed a computational platform called Personal Antigen Selection Calculator (PASCal) that identifies frequently presented immunogenic peptide sequences built on HLA-genetics and tumor profile of thousands of real individuals.3 Here we show the performance of PASCal for the identification of both shared and personalized tumor targets in metastatic colorectal cancer (mCRC) and breast cancer subjects.MethodsExpression frequency of the tumor-specific antigens (TSAs) ranked in PASCal’s database (based on 7,548 CRC specimen) was compared to the RNA-sequencing data of CRC tumors obtained from TCGA. Using PASCal, 12 shared PEPIs (epitopes restricted to at least 3 HLA class I alleles of a subject from an in silico cohort) derived from 7 TSAs were selected as frequent targets (calculated probability: average 2.5 [95%CI 2.4–2.8] TSAs/patient). Spontaneous immune responses against each of the twelve 9mer peptides were determined by ELISpot using PBMCs of 10 mCRC subjects who participated in the OBERTO-101 study.4 PEPIs selected for a breast cancer subject based on her HLA genotype were also tested.ResultsEach of the 106 tumors analyzed expressed at least 13, average 15 of the 20 top-ranked TSAs in PASCal’s database confirming their prevalence in CRC. 7/10 subjects had spontaneous CD8+ T-cell responses against at least one peptide selected with PASCal. Each peptide (12/12) was recognized by at least one patient. Patients‘ T-cells reacted with average 3.6/12 (30%) peptides confirming the expression of average 2.8 [95%CI 1.0–4.6] TSAs (n=10). After HLA-matching, among the subjects for whom we could select at least 4 PEPIs (average 5) from the list of 12 peptides (n=6), average 2.5 (50%) peptides were positive. Of the 12 PEPIs selected with PASCal for a breast cancer subject, we detected spontaneous T-cell responses against 9 PEPIs, indicating that at least 75% of the selected peptides were present in the subject’s tumor and were recognized by T-cells.ConclusionsPASCal platform accommodates both tumor- and patient heterogeneity and identifies non-mutated tumor targets that may trigger polyclonal cytotoxic T-cell responses. It is a rapid tool for the design of both off-the-shelf and personalized cancer vaccines negating the need for tumor biopsy.ReferencesWells DK, van Buuren MM, Dang KK, et al. Key parameters of tumor epitope immunogenicity revealed through a consortium approach improve neoantigen prediction. Cell 2020:183(3):818–34.e13.Bulik-Sullivan B, Busby J, Palmer CD, et al. Deep learning using tumor HLA peptide mass spectrometry datasets improves neoantigen identification. Nat Biotech 2018:37:55–63.Somogyi E, Csiszovszki Z, Lorincz O, et al. 1181PDPersonal antigen selection calculator (PASCal) for the design of personal cancer vaccines. Annal Oncol 2019:30(Supplement_5):v480-v81.Hubbard J, Cremolini C, Graham R, et al. P329 PolyPEPI1018 off-the shelf vaccine as add-on to maintenance therapy achieved durable treatment responses in patients with microsatellite-stable metastatic colorectal cancer patients (MSS mCRC). J ImmunoTher Cancer 2019:7(1):282.

scholarly journals Cross-Priming of T Cell Responses by Synthetic Microspheres Carrying a CD8+ T Cell Epitope Requires an Adjuvant Signal

2005 ◽  
Vol 174 (6) ◽  
pp. 3432-3439 ◽  
Author(s):  
Florence Boisgérault ◽  
Paloma Rueda ◽  
Cheng Ming Sun ◽  
Sandra Hervas-Stubbs ◽  
Marie Rojas ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Epitope ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
T Cell Epitope ◽  
Cell Responses

scholarly journals Induction of Polyomavirus-Specific CD8+T Lymphocytes by Distinct Dendritic Cell Subpopulations

2001 ◽  
Vol 75 (1) ◽  
pp. 544-547 ◽  
Author(s):  
Donald R. Drake ◽  
Mandy L. Shawver ◽  
Annette Hadley ◽  
Eric Butz ◽  
Charles Maliszewski ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
Cell Epitope ◽  
T Cell Responses ◽  
T Cell Epitope ◽  
Cell Responses ◽  
Cd8 T Lymphocytes ◽  
Cell Subpopulations ◽  
Antigen Presenting

ABSTRACT Dendritic cells are pivotal antigen-presenting cells for generating adaptive T-cell responses. Here, we show that dendritic cells belonging to either the myeloid-related or lymphoid-related subset are permissive for infection by mouse polyomavirus and, when loaded with a peptide corresponding to the immunodominant anti-polyomavirus CD8+T-cell epitope or infected by polyomavirus, are each capable of driving expansion of primary polyomavirus-specific CD8+ T-cell responses in vivo.

Identification of T Cell Epitope of ADAMTS13 in Thrombotic Thrombocytopenic Purpura Patients

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 106-106 ◽  
Author(s):  
Laurent Gilardin ◽  
Sandrine Delignat ◽  
Bernard Maillere ◽  
Bagirath Gangadharan ◽  
Ivan Peyron ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Line ◽  
Cd4 T Cells ◽  
Binding Capacity ◽  
Cell Epitope ◽  
Interferon Γ ◽  
Cd4 T Cell ◽  
T Cell Epitope ◽  
T Cell Lines

Abstract Introduction: Thrombotic Thrombocytopenic Purpura (TTP) results from the development of auto-antibodies directed against A Disintegrin And Metalloproteinase with Thrombospondin type 1 repeats, 13th member (A13). The implication of CD4+ T-cells in the pathogenesis of the disease is suggested by the existence of a restriction to HLA DRB1*11 allele and by the isotype switch of the antibodies. However, T-cell autoimmune response to A13 and the properties of CD4+ T-cells from TTP patients have never been studied. Here, we determined the immunodominant T-cell epitope of A13 in TTP patients. Methods: Using the IEDB website, we predicted in silico the immunodominant peptides of A13 based on their binding capacity to HLA DR11 haplotype. Subsequently, these peptides were synthesized and validated in vitro for their binding capacity to purified HLA-DR11 molecules using an ELISA competitive assay. The peptides that bound with the best capacity to HLA-DRB1*11 molecule were then tested for their recognition by human CD4+ T-cells from HLA DRB1*11 healthy donors and patients, at diagnosis or in remission. To this end, CD4+ T-cells were repetitively stimulated with HLA-DRB1*11 monocyte-derived dendritic cells loaded with the peptides and T-cell line were generated after amplification of interferon-γ secreting cells selected upon stimulation. The effect of individual peptide on activation of the established CD4+ T-cell line was assessed by interferon-γ (IFNγ) ELISPOT. Next, we evaluated the promiscuous HLA-binding capacity of the DRB1*11 identified peptides using the same method in HLA DRB1*01 TTP patients. Finally, in order to validate the involvement of these peptides in an immune response toward A13 in vivo, we immunized a humanized HLA DRB1*01-transgenic H-2 class I-/class II-knockout mouse with full length recombinant human A13 (rhA13). We then generated A13-specific T-cell hybridomas restricted to human HLA DRB1*01 and investigated whether the peptides previously identified were recognized by the hybridomas. Results A first list of 48 peptides with reliable predicted binding scores was elaborated through IEDB analysis. Of these, twenty-one peptides demonstrated a high binding capacity to HLA DRB1*11 molecules on ELISA competitive assay. These were selected to stimulate human CD4+ T-cells and we generated CD4+ T-cell lines from HLA DRB1*11 healthy donors and patients (n=5). Six A13 derived peptides were able to activate CD4+ T-cell lines, as revealed by IFNγ secretion by ELISPOT. The peptides were identified to be located within different domains of the protein but more particularly in the spacer and CUB2 domains. Interestingly, two of the identified peptides demonstrated promiscuity based on their ability to activate a CD4+ T-cell line we generated from a HLA DRB1*01 TTP patient. In parallel studies, using HLA DRB1*01 transgenic mice immunized with rhA13, we generated A13-specific T-cell hybridomas. The screening of their specificity allowed us to identify only one A13 derived peptide. The sequence of the peptide, located within the CUB2 domain, was precisely determined, it is promiscuous between DRB1*01 and DRB1*11 haplotype and represents the immunodominant CD4+ T-cell epitope of ADAMTS13. Conclusion: We identified several undescribed CD4+T-cell epitopes of A13 in HLA DRB1*1101 patients. They are located in different domains of the protein, particularly in the spacer and CUB2 domains. One of them, located in the CUB2 domain, is promiscuous to HLA DRB1*0101 and responsible for the immunodominant response to A13. The results we obtained, lead us to generate the tools to study the specific cells involved in the origin of the physiopathological process of the disease. Disclosures Coppo: Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees.

scholarly journals An Arthritis-Suppressive and Treg Cell-Inducing CD4+ T Cell Epitope Is Functional in the Context of HLA-Restricted T Cell Responses

2016 ◽  
Vol 68 (3) ◽  
pp. 639-647 ◽  
Author(s):  
Charlotte de Wolf ◽  
Ruurd van der Zee ◽  
Ineke den Braber ◽  
Tibor Glant ◽  
Bernard Maillère ◽  
...  
Keyword(s):  
T Cell ◽  
Treg Cell ◽  
Cell Epitope ◽  
T Cell Responses ◽  
Cd4 T Cell ◽  
T Cell Epitope ◽  
Cell Responses
Sign in / Sign up

Export Citation Format

Share Document