Quantification of the preexisting CD4 T-cell repertoire specific for human erythropoietin reveals its immunogenicity potential

Delluc, Stéphanie; Ravot, Gilles; Maillère, Bernard

doi:10.1182/blood-2010-04-280875

Cited by 40 publications

(50 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…As previously published (34,35,40), the yield of peptide T cell lines isolated in vitro depends on the frequency of pre-existing peptidespecific T cells present in the blood donors. We therefore estimated the frequencies of pre-existing Lipo5-specific CD4 T cells, as previously described (34,35,40). A mean of 2.79 precursors per million was found for G2, whereas the frequency of precursors was below 1 cell per million for the other peptides.…”

Section: Discussionmentioning

confidence: 88%

Hierarchy of CD4 T Cell Epitopes of the ANRS Lipo5 Synthetic Vaccine Relies on the Frequencies of Pre-Existing Peptide-Specific T Cells in Healthy Donors

Castelli

Szely

Olivain

et al. 2013

The Journal of Immunology

View full text Add to dashboard Cite

The Agence National de Recherche sur le SIDA et les hepatitis Lipo5 vaccine is composed by five long fragments of HIV proteins and was recently shown to induce in seronegative volunteers a CD4 T cell response largely dominated by the G2 fragment. To understand this response profile, we submitted the five HIV fragments to HLA-DR–binding assays and evaluated the frequency of naive Lipo5-specific CD4 T lymphocytes in the blood of 22 healthy individuals. We enumerated the Lipo5-specific T cell lines induced in vitro by weekly rounds of specific stimulation. Four peptides and hence not only G2 exhibited a broad specificity for HLA-DR molecules. In contrast, most of the T cell lines specific for Lipo5 reacted with G2, revealing a G2-specific T cell repertoire superior to 2 cells per million, whereas it is close to 0.4 for the other peptides. We also found good cross-reactivity of all the peptides with clade B and C variants and that G2 and P1 are able to recruit T cells that recognize HIV-infected cells. We therefore mainly observed very good concordance between the frequency to individual Lipo5 peptides among vaccinees in a large-scale vaccine trial and the distribution of peptide specificity of the in vitro induced T cell lines. These findings underline the role of the size of the epitope-specific naive repertoire in shaping the CD4 T cell response after vaccination and highlight the value of evaluating the naive repertoire to predict vaccine immunogenicity.

show abstract

Section: Discussionmentioning

confidence: 88%

Hierarchy of CD4 T Cell Epitopes of the ANRS Lipo5 Synthetic Vaccine Relies on the Frequencies of Pre-Existing Peptide-Specific T Cells in Healthy Donors

Castelli

Szely

Olivain

et al. 2013

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…In our assays, the yield of T cell lines depends on the number of preexisting T cells in the blood of the donors at the initiation of the T cell culture. It was not the goal of this study to evaluate the size of the MDK-specific T cell repertoire, as we have already described for other proteins (41)(42)(43), but the low yield of T cell lines suggests that there were few preexisting CD4 ϩ T cells specific for the mature form of MDK. A low level of MDK is detected in normal subjects (44), and this residual expression may contribute to reduce the MDK T cell repertoire.…”

Section: Discussionmentioning

confidence: 98%

“…A low level of MDK is detected in normal subjects (44), and this residual expression may contribute to reduce the MDK T cell repertoire. According to others (45,46), injection of recombinant MDK is expected to induce a CD4 ϩ T cell response in humans beings with a limited amplitude and consequently be poorly immunogenic (42,43,47). This could be an advantage for therapeutic applications of the MDK protein to treat cardiac ischemia (48) and neuronal disorders (49).…”

Section: Discussionmentioning

confidence: 99%

The Signal Peptide of the Tumor-shared Antigen Midkine Hosts CD4+ T Cell Epitopes

Kerzerho¹,

Schneider²,

Favry³

et al. 2013

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background: The CD4 T cell response to the tumor antigen Midkine was unknown. Results: Most of the T cell response to Midkine relies on T cell epitopes contained in its signal peptide. Conclusion:The signal peptide of Midkine is accessible to HLA class II pathway for CD4 T cell presentation. Significance: It is a new function for signal peptides to contribute to tumor-specific CD4 T cell response.

show abstract

“…• Les tests prédictifs d'activation des lymphocytes T CD4 humains sont les plus informatifs pour prédire l'immunogénicité des protéines [16,17]. Leur principe consiste à détecter, dans le sang de sujets normaux possédant des HLA différents, la présence de lymphocytes T CD4 spécifiques des protéines thérapeutiques.…”

Section: Méthodes D'évaluation De La Réponse Des Lymphocytes Tunclassified

“…De fait, les mesures prises pour éviter l'altération des lots d'EPO, telles que l'enrobage du caoutchouc des seringues et le respect de la chaîne du froid, ont permis de revenir aux taux initiaux d'érythroblastopénie. Sachant que la réponse humorale dirigée contre l'EPO est dépendante de lymphocytes T CD4, nous avons étudié le répertoire de lymphocytes T CD4 préexistants spécifiques de l'EPO chez des sujets normaux en utilisant la te chnique d'amplification de ces cellules in vitro [16]. Nous avons observé que ce répertoire était relativement important chez près de la moitié des donneurs sains étudiés.…”

Section: Méthodes D'évaluation De La Réponse Des Lymphocytes Tunclassified

La prédiction de l’immunogénicité des protéines thérapeutiques

Maillère

Delluc

Ravot³

2012

Med Sci (Paris)

Self Cite

View full text Add to dashboard Cite

Quantification of the preexisting CD4 T-cell repertoire specific for human erythropoietin reveals its immunogenicity potential

Cited by 40 publications

References 24 publications

Hierarchy of CD4 T Cell Epitopes of the ANRS Lipo5 Synthetic Vaccine Relies on the Frequencies of Pre-Existing Peptide-Specific T Cells in Healthy Donors

Hierarchy of CD4 T Cell Epitopes of the ANRS Lipo5 Synthetic Vaccine Relies on the Frequencies of Pre-Existing Peptide-Specific T Cells in Healthy Donors

The Signal Peptide of the Tumor-shared Antigen Midkine Hosts CD4+ T Cell Epitopes

La prédiction de l’immunogénicité des protéines thérapeutiques

Contact Info

Product

Resources

About