A recombinant human HLA-class I antigen linked to dextran elicits innate and adaptive immune responses

Schøller, Jørgen; Singh, Mahavir; Bergmeier, Lesley A.; Brunstedt, Katja; Wang, Yufei; Whittall, Trevor; Rahman, Durdana; Lehner, Thomas

doi:10.1016/j.jim.2010.05.008

Cited by 16 publications

(20 citation statements)

References 28 publications

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“…MHC multimers are ideal to verify whether the T cells of interest recognize the particular MHC–peptide complex, and to assess the amount of specific T cells. MHC-multimers are most commonly used in the original form, as tetramers [52]; however, several variants have been made with higher number MHC–peptide complexes per entity (e.g., as pentamers or dextramers [53,54], or improved functionality in the form of streptamers [55]). In the end, however, it can be hard to estimate whether a given epitope is actually presented on infected or malign cells.…”

Section: Experimental Approaches For T-cell Epitope Discovery Detectmentioning

confidence: 99%

Predictions versus high-throughput experiments in T-cell epitope discovery: competition or synergy?

Lundegaard

Lund²,

Nielsen

2012

Expert Review of Vaccines

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Prediction methods as well as experimental methods for T-cell epitope discovery have developed significantly in recent years. High-throughput experimental methods have made it possible to perform full-length protein scans for epitopes restricted to a limited number of MHC alleles. The high costs and limitations regarding the number of proteins and MHC alleles that are feasibly handled by such experimental methods have made in silico prediction models of high interest. MHC binding prediction methods are today of a very high quality and can predict MHC binding peptides with high accuracy. This is possible for a large range of MHC alleles and relevant length of binding peptides. The predictions can easily be performed for complete proteomes of any size. Prediction methods are still, however, dependent on good experimental methods for validation, and should merely be used as a guide for rational epitope discovery. We expect prediction methods as well as experimental validation methods to continue to develop and that we will soon see clinical trials of products whose development has been guided by prediction methods.

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Section: Experimental Approaches For T-cell Epitope Discovery Detectmentioning

confidence: 99%

Predictions versus high-throughput experiments in T-cell epitope discovery: competition or synergy?

Lundegaard

Lund²,

Nielsen

2012

Expert Review of Vaccines

View full text Add to dashboard Cite

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“…Four HLA class I alleles and one HLA class II allele were selected, as they are common in the Caucasian population (8), their peptide folding is known, and they are likely to stimulate an alloantibody response in the majority of humans (shown together with their respective folding peptide in parentheses): (i) HLA-A*01:01(IVDCLTEMY), (ii) HLA-A*02:01(GLIQLVE GV), (iii) HLA-A*03:01(RIAAWMATY), (iv) HLA-A*11:01(VTDFSVIK), and (v) HLA-DRB1*04:01. Preparation of recombinant HLA class I heavy chains and ␤2 microglobulin (␤2 M) was described in detail elsewhere (32). Briefly, synthetic genes encoding the protein-coding sequence minus the signal peptide and transmembrane regions of the human MHC class I alleles were created by PCR of overlapping DNA primers based on GenBank sequence information.…”

Section: Methodsmentioning

confidence: 99%

“…For preparation of the dextramer vaccine complexes, the biotinylated peptide-MHC class I and class II complexes, trimeric HIVgp140, SIVp27, and Hsp70 359-609 were linked to a streptavidin-coated, divinyl sulfone acid-activated dextran backbone (32).…”

Section: Methodsmentioning

confidence: 99%

Immunization with Recombinant HLA Classes I and II, HIV-1 gp140, and SIV p27 Elicits Protection against Heterologous SHIV Infection in Rhesus Macaques

Mörner

Jansson

Bunnik

et al. 2011

J Virol

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Major histocompatibility complex (MHC) molecules expressed on the surface of human immunodeficiency virus (HIV) are potential targets for neutralizing antibodies. Since MHC molecules are polymorphic, nonself MHC can also be immunogenic. We have used combinations of novel recombinant HLA class I and II and HIV/simian immunodeficiency virus (SIV) antigens, all linked to dextran, to investigate whether they can elicit protective immunity against heterologous simian/human immunodeficiency virus (SHIV) challenge in rhesus macaques. Three groups of animals were immunized with HLA (group 1, n ‫؍‬ 8), trimeric YU2 HIV type 1 (HIV-1) gp140 and SIV p27 (HIV/SIV antigens; group 2, n ‫؍‬ 8), or HLA plus HIV/SIV antigens (group 3, n ‫؍‬ 8), all with Hsp70 and TiterMax Gold adjuvant. Another group (group 4, n ‫؍‬ 6) received the same vaccine as group 3 without TiterMax Gold. Two of eight macaques in group 3 were completely protected against intravenous challenge with 18 50% animal infective doses (AID 50 ) of SHIV-SF162P4/C grown in human cells expressing HLA class I and II lineages represented in the vaccine, while the remaining six macaques showed decreased viral loads compared to those in unimmunized animals. Complement-dependent neutralizing activity in serum and high levels of anti-HLA antibodies were elicited in groups 1 and 3, and both were inversely correlated with the plasma viral load at 2 weeks postchallenge. Antibody-mediated protection was strongly supported by the fact that transfer of pooled serum from the two challenged but uninfected animals protected two naïve animals against repeated low-dose challenge with the same SHIV stock. This study demonstrates that immunization with recombinant HLA in combination with HIV-1 antigens might be developed into an alternative strategy for a future AIDS vaccine.

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“…This can result in a weak staining of autoreactive clones. To overcome this problem MHC dextramers have been recently introduced [66,67]. MHC dextramers are MHC-peptide complexes bound to a dextran polymer backbone.…”

Section: Advances In T Cell Immune Monitoringmentioning

confidence: 99%

Monitoring Inflammation, Humoral and Cell-mediated Immunity in Pancreas and Islet Transplants

Monti

Vignali

Piemonti

2015

CDR

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Type 1 diabetes (T1D) is caused by the chronic autoimmune destruction of insulin producing beta cells. Beta cell replacement therapy through whole pancreas or islet transplantation is a therapeutic option for patients in which a stable glucose control is not achievable with exogenous insulin therapy. Long-term insulin independence is, however, hampered by the recipient immune response that includes activation of inflammatory pathways and specific allo- and auto-immunity. The identification and monitoring of soluble and cellular biomarkers are of critical relevance for the prediction of graft damage, for the evaluation of responses to immune-modulating therapy, and for target pathways identification to generate novel drugs or therapeutic approaches. The final objective of immune monitoring is to find ways to improve the outcome of pancreas and islet transplantation. In this review, we discuss the available tools to monitor the innate, humoral and cellular responses after islet and pancreas transplantation, and the most relevant findings generated by these measurements.

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A recombinant human HLA-class I antigen linked to dextran elicits innate and adaptive immune responses

Cited by 16 publications

References 28 publications

Predictions versus high-throughput experiments in T-cell epitope discovery: competition or synergy?

Predictions versus high-throughput experiments in T-cell epitope discovery: competition or synergy?

Immunization with Recombinant HLA Classes I and II, HIV-1 gp140, and SIV p27 Elicits Protection against Heterologous SHIV Infection in Rhesus Macaques

Monitoring Inflammation, Humoral and Cell-mediated Immunity in Pancreas and Islet Transplants

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