Identification of alloreactive T-cell epitopes on the Rhesus D protein

Slides:

Advertisements

Similar presentations

Supplementary Figure 2 Anti-PD-L1 (avelumab) enhances CD8 activation and decreases CD4 to a greater extent than commercially available anti-PD-L1 blocking.

Advertisements

T-cell responses associated with neonatal alloimmune thrombocytopenia: isolation of HPA-1a–specific, HLA-DRB3*0101–restricted CD4+ T cells by Maria Therese.

Increased apoptosis of peripheral blood T cells following allogeneic hematopoietic cell transplantation by Ming-Tseh Lin, Li-Hui Tseng, Haydar Frangoul,

GVHD-associated immunodeficiency: soil or seed?

AAV-1–mediated gene transfer to skeletal muscle in humans results in dose-dependent activation of capsid-specific T cells by Federico Mingozzi, Janneke.

Engineering Human Peripheral Blood Stem Cell Grafts that Are Depleted of Naïve T Cells and Retain Functional Pathogen-Specific Memory T Cells Marie Bleakley,

TCR-MHC-peptide(s): in vivo veritas

Depletion of Alloreactive Donor T Lymphocytes by CD95-Mediated Activation-Induced Cell Death Retains Antileukemic, Antiviral, and Immunoregulatory T Cell.

by Jacob Rachmilewitz, Gregory J

by Masih Ostad, Margareta Andersson, Astrid Gruber, and Anne Sundblad

Low-level HLA antibodies do not predict platelet transfusion failure in TRAP study participants by Rachael P. Jackman, Xutao Deng, Douglas Bolgiano, Mila.

Molecular Typing Shows a High Level of HLA Class I Incompatibility in Serologically Well Matched Donor/Patient Pairs: Implications for Unrelated Bone Marrow.

Human CD1c+ dendritic cells secrete high levels of IL-12 and potently prime cytotoxic T-cell responses by Giulia Nizzoli, Jana Krietsch, Anja Weick, Svenja.

Aurora-A kinase: a novel target of cellular immunotherapy for leukemia

Further Analysis of Interleukin-2 Receptor Subunit Expression on the Different Human Peripheral Blood Mononuclear Cell Subsets by Denis David, Lynda Bani,

Mesenchymal stem cells ameliorate experimental autoimmune encephalomyelitis inducing T-cell anergy by Emanuela Zappia, Simona Casazza, Enrico Pedemonte,

Key amino acid positions identified by association analysis are highlighted in three-dimensional ribbon models for the HLA-DR, HLA-DQ, HLA-A and HLA-DP.

Maintenance of HCV-specific T-cell responses in antibody-deficient patients a decade after early therapy by Nasser Semmo, Michaela Lucas, George Krashias,

Working together to block alloimmunization

FVIII proteins with a modified immunodominant T-cell epitope exhibit reduced immunogenicity and normal FVIII activity by Ruth A. Ettinger, Joseph A. Liberman,

Ex vivo induction of multiple myeloma–specific cytotoxic T lymphocytes

Rapid generation of combined CMV-specific CD4+ and CD8+ T-cell lines for adoptive transfer into recipients of allogeneic stem cell transplants by Georg.

Immunologic evidence for lack of heterologous protection following resolution of HCV in patients with non–genotype 1 infection by Julian Schulze zur Wiesch,

Antigen Presenting Phenotype of Hodgkin Reed-Sternberg Cells: Analysis of the HLA Class I Processing Pathway and the Effects of Interleukin-10 on Epstein-Barr.

Increased survival is a selective feature of human circulating antigen-induced plasma cells synthesizing high-affinity antibodies by Inés González-García,

Dendritic cells are functionally defective in multiple myeloma: the role of interleukin-6 by Marina Ratta, Francesco Fagnoni, Antonio Curti, Rosanna Vescovini,

Mature dendritic cells pulsed with freeze–thaw cell lysates define an effective in vitro vaccine designed to elicit EBV-specific CD4+ and CD8+ T lymphocyte.

Rare cells predict GVHD

HLA-A*0201+ Plasmacytoid Dendritic Cells Provide a Cell-Based Immunotherapy for Melanoma Patients Caroline Aspord, Marie-Therese Leccia, Dimitri Salameire,

Peripheral blood lymphocytes genetically modified to express the self/tumor antigen MAGE-A3 induce antitumor immune responses in cancer patients by Raffaella.

Immunologic potential of donor lymphocytes expressing a suicide gene for early immune reconstitution after hematopoietic T-cell–depleted stem cell transplantation.

Lymphoma spread? Target CD47-SIRPα!

Cytomegalovirus-specific T cells are primed early after cord blood transplant but fail to control virus in vivo by Suzanne M. McGoldrick, Marie E. Bleakley,

A recombinant bispecific single-chain antibody, CD19 × CD3, induces rapid and high lymphoma-directed cytotoxicity by unstimulated T lymphocytes by Anja.

Tumor-Specific Human CD4+ Regulatory T Cells and Their Ligands

by Vladia Monsurrò, Ena Wang, Yoshisha Yamano, Stephen A

FLT3 ligand administration after hematopoietic cell transplantation increases circulating dendritic cell precursors that can be activated by CpG oligodeoxynucleotides.

Expression of ectonucleotidase CD39 by Foxp3+ Treg cells: hydrolysis of extracellular ATP and immune suppression by Giovanna Borsellino, Markus Kleinewietfeld,

Identification of a Coordinated CD8 and CD4 T Cell Response Directed Against Mismatched HLA Class I Causing Severe Acute Graft-versus-Host Disease Avital.

Vaccination regimens incorporating CpG-containing oligodeoxynucleotides and IL-2 generate antigen-specific antitumor immunity from T-cell populations undergoing.

Mutated regions of nucleophosmin 1 elicit both CD4+ and CD8+ T-cell responses in patients with acute myeloid leukemia by Jochen Greiner, Yoko Ono, Susanne.

Volume 7, Issue 3, Pages (September 1997)

Induction of chronic lymphocytic leukemia (CLL)–specific CD4- and CD8-mediated T-cell responses using RNA-transfected dendritic cells by Martin R. Müller,

Characterization of human memory CD4+ T-cell responses to the dog allergen Can f 4 Aino L. Rönkä, MD, Tuure T. Kinnunen, MD, PhD, Amélie Goudet, BSc,

HLA-A*0201+ Plasmacytoid Dendritic Cells Provide a Cell-Based Immunotherapy for Melanoma Patients Caroline Aspord, Marie-Therese Leccia, Dimitri Salameire,

A function-blocking PAR4 antibody is markedly antithrombotic in the face of a hyperreactive PAR4 variant by Shauna L. French, Claudia Thalmann, Paul F.

A. Haggar, J.-I. Flock, A. Norrby-Teglund

Volume 39, Issue 4, Pages (October 2003)

Protein information in the Human Protein Atlas.

Tetramer staining performed to determine frequencies of epitope-specific T cells after clearance of HPV16 infection but prior to isolation of T-cell clones.

by Anja Freese, and Nicholas Zavazava

Soluble CD86 Is a Costimulatory Molecule for Human T Lymphocytes

Heterogeneous MHC II Restriction Pattern of Autoreactive Desmoglein 3 Specific T Cell Responses in Pemphigus Vulgaris Patients and Normals Michael Hertl,

Volume 13, Issue 2, Pages (February 2006)

by Wanqiu Hou, James S. Gibbs, Xiuju Lu, Christopher B

T-cell assays confirm immunogenicity of tungsten-induced erythropoietin aggregates associated with pure red cell aplasia by Tina Rubic-Schneider, Masataka.

Functional analysis of clinical response to low-dose IL-2 in patients with refractory chronic graft-versus-host disease by Jennifer S. Whangbo, Haesook.

by Defne Bayik, Debra Tross, Lydia A

Phenotype of rTT.C-specific plasma blasts.

Effects of daratumumab on natural killer cells and impact on clinical outcomes in relapsed or refractory multiple myeloma by Tineke Casneuf, Xu Steven.

Defining antigen-specific responses with human MHC class II tetramers

Ex vivo depletion of alloreactive cells based on CFSE dye dilution, activation antigen selection, and dendritic cell stimulation by Wayne R. Godfrey, Mark.

Tumor-Specific Human CD4+ Regulatory T Cells and Their Ligands

Volume 115, Issue 4, Pages (October 1998)

by Honglin Chen, Paul Smith, Richard F. Ambinder, and S. Diane Hayward

ALT-803 stimulates proliferation and activation of human NK cells and T cells in vitro. ALT-803 stimulates proliferation and activation of human NK cells.

Representative cytokine and cytotoxicity responses to CMV peptides on day 0 and day 7 in one HLA A2+ donor. Representative cytokine and cytotoxicity responses.

Immunologic and pharmacokinetic studies.

Patient Tregs express normal levels of suppression.

HLA-C Level Is Regulated by a Polymorphic Oct1 Binding Site in the HLA-C Promoter Region Nicolas Vince, Hongchuan Li, Veron Ramsuran, Vivek Naranbhai,

Presentation transcript:

Identification of alloreactive T-cell epitopes on the Rhesus D protein by Lisa-Marie Stott, Robert N. Barker, and Stanislaw J. Urbaniak Blood Volume 96(13):4011-4019 December 15, 2000 ©2000 by American Society of Hematology

PBMCs from all RhD-negative donors alloimmunized with RhD-positive RBCs proliferate in response to peptides from the sequence of the RhD protein.PBMCs were obtained from representative alloimmune donors 2 (A), 8 (B), and 13 (C) and tested for their ability ... PBMCs from all RhD-negative donors alloimmunized with RhD-positive RBCs proliferate in response to peptides from the sequence of the RhD protein.PBMCs were obtained from representative alloimmune donors 2 (A), 8 (B), and 13 (C) and tested for their ability to proliferate against the panel of peptides spanning the RhD protein. In each case, all the peptides were tested on a single occasion, and the broken line indicates the level of proliferation assumed to represent a positive response (the higher of SI = 3 or cpm = 1000). Lisa-Marie Stott et al. Blood 2000;96:4011-4019 ©2000 by American Society of Hematology

The pattern of RhD peptides that stimulate PBMCs from alloimmune donors to proliferate is reproducible.Proliferative responses of PBMCs from alloimmune donor 12 against the panel of peptides spanning the RhD protein were compared on 2 occasions (A and B) 2 ... The pattern of RhD peptides that stimulate PBMCs from alloimmune donors to proliferate is reproducible.Proliferative responses of PBMCs from alloimmune donor 12 against the panel of peptides spanning the RhD protein were compared on 2 occasions (A and B) 2 months apart. The broken line indicates the level of proliferation assumed to represent a positive response (the higher of SI = 3 or cpm = 1000). Lisa-Marie Stott et al. Blood 2000;96:4011-4019 ©2000 by American Society of Hematology

Variation in the number of RhD peptides that stimulate PBMCs from alloimmune donors to proliferate is strongly correlated with the level of anti-D antibody in their serum.Shown is the relation (Rs = 0.75; P < .003) between the number of RhD peptides that el... Variation in the number of RhD peptides that stimulate PBMCs from alloimmune donors to proliferate is strongly correlated with the level of anti-D antibody in their serum.Shown is the relation (Rs = 0.75; P < .003) between the number of RhD peptides that elicited proliferation of PBMCs from each of the deliberately alloimmunized donors (1-13) and the level of anti-D antibody in their serum. If antibody concentrations were measured more than once during the period in which PBMC samples were obtained, the highest level was recorded. Lisa-Marie Stott et al. Blood 2000;96:4011-4019 ©2000 by American Society of Hematology

PBMCs from control RhD-negative donors, who have not been alloimmunized, rarely proliferate when stimulated with peptides from the RhD protein sequence.Shown here are the proliferative responses of PBMCs from 3 control unimmunized RhD-negative donors (A, B,... PBMCs from control RhD-negative donors, who have not been alloimmunized, rarely proliferate when stimulated with peptides from the RhD protein sequence.Shown here are the proliferative responses of PBMCs from 3 control unimmunized RhD-negative donors (A, B, and C) against the panel of peptides spanning the RhD protein. The broken line indicates the level of proliferation assumed to represent a positive response (the higher of SI = 3 or cpm = 1000). Lisa-Marie Stott et al. Blood 2000;96:4011-4019 ©2000 by American Society of Hematology

The proliferation of PBMCs from alloimmune donors against RhD peptides is mediated by T cells.Shown are the proliferative responses of purified peripheral blood T cells from a representative alloimmune donor (22) against the smaller panel of peptides spanni... The proliferation of PBMCs from alloimmune donors against RhD peptides is mediated by T cells.Shown are the proliferative responses of purified peripheral blood T cells from a representative alloimmune donor (22) against the smaller panel of peptides spanning the RhD protein. The apparent discrepancy with the sequences that stimulated PBMCs from this donor (Table 2) was due to differences in the peptide panels screened and the greater responsiveness of the purified T cells. Thus, the T cells were not tested against 2 (17 and 28) of the 3 peptides (2, 17, and 28) that elicited proliferation of PBMCs from the same donor, and PBMCs did respond to 4 of the peptides (5, 8, 12, and 47) that stimulated the T cells, but the response was not strong enough to represent a significant difference. Lisa-Marie Stott et al. Blood 2000;96:4011-4019 ©2000 by American Society of Hematology

The proliferation of T cells from alloimmune donors against RhD peptides depends on HLA class II molecules.Cultures of PBMCs from a representative donor (6) were stimulated with RhD peptide, and class II–restricted responses were blocked by the addition of ... The proliferation of T cells from alloimmune donors against RhD peptides depends on HLA class II molecules.Cultures of PBMCs from a representative donor (6) were stimulated with RhD peptide, and class II–restricted responses were blocked by the addition of antibody specific for DP, DQ, DR, or DR15. ▪, no antigen; ■, RhD peptide 17. Lisa-Marie Stott et al. Blood 2000;96:4011-4019 ©2000 by American Society of Hematology

T cells from alloimmune donors that proliferate against RhD peptides in vitro were, with few exceptions, previously activated in vivo.Shown here are the proliferative responses of CD45RO+ (▪, previously activated) and CD45RA+ (■, previously inactive) T cell... T cells from alloimmune donors that proliferate against RhD peptides in vitro were, with few exceptions, previously activated in vivo.Shown here are the proliferative responses of CD45RO+ (▪, previously activated) and CD45RA+ (■, previously inactive) T cells from alloimmune donors 12 (A), 17 (B), and 4 (C,D) against selected RhD peptides. Lisa-Marie Stott et al. Blood 2000;96:4011-4019 ©2000 by American Society of Hematology

Particular peptides from the RhD protein stimulate T cells from most alloimmune donors to proliferate.Shown here is the proportion of alloimmune donors (n = 22; for peptides 34, 35, and 36, n = 5, since original results obtained using sequence Ile218 were o... Particular peptides from the RhD protein stimulate T cells from most alloimmune donors to proliferate.Shown here is the proportion of alloimmune donors (n = 22; for peptides 34, 35, and 36, n = 5, since original results obtained using sequence Ile218 were omitted) with T cells that proliferated in response to each of the 68 peptides from the panel spanning the RhD protein. Lisa-Marie Stott et al. Blood 2000;96:4011-4019 ©2000 by American Society of Hematology

RhD protein sequences that stimulate T cells from alloimmune donors to proliferate are not limited to extracellular loops.The predicted topographic features of the RhD protein5 6illustrate the location of the 4 dominant RhD peptides that elicited proliferat... RhD protein sequences that stimulate T cells from alloimmune donors to proliferate are not limited to extracellular loops.The predicted topographic features of the RhD protein5 6illustrate the location of the 4 dominant RhD peptides that elicited proliferation by T cells from most of the alloimmune donors. Residues within dominant peptides, ● (peptide 6 aa52-66, peptide 13 aa97-111, peptide 17 aa117-131, and peptide 28 aa177-191). Lisa-Marie Stott et al. Blood 2000;96:4011-4019 ©2000 by American Society of Hematology