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Identification of immunodominant CD4-restricted epitopes co-located with antibody binding sites in individuals vaccinated with ALVAC-HIV and AIDSVAX B/E.

Ratto-Kim S, de Souza MS, Currier JR, Karasavvas N, Sidney J, Rolland M, Valencia-Micolta A, Madnote S, Sette A, Nitayaphan S, Pitisuttuthum P, Kaewkungwal J, Rerks-Ngarm S, O'Connell R, Michael N, Robb ML, Marovich M, Kim JH - PLoS ONE (2015)

Bottom Line: Non-transformed Env-specific T cell lines established from RV144 vaccinees were used to determine the fine epitope mapping of the V2 and C1 responses and the HLA class II restriction.Data showed that there are two CD4+ epitopes contained within the V2 loop: one encompassing the α4β7 integrin binding site (AA179-181) and the other nested between two previously described genetic sieve signatures (AA169, AA181).There was no correlation between the frequencies of CD4+ fine epitope responses and binding antibody.

View Article: PubMed Central - PubMed

Affiliation: United States Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, 20910, United States of America.

ABSTRACT
We performed fine epitope mapping of the CD4+ responses in the ALVAC-HIV-AIDSVAX B/E prime-boost regimen in the Thai Phase III trial (RV144). Non-transformed Env-specific T cell lines established from RV144 vaccinees were used to determine the fine epitope mapping of the V2 and C1 responses and the HLA class II restriction. Data showed that there are two CD4+ epitopes contained within the V2 loop: one encompassing the α4β7 integrin binding site (AA179-181) and the other nested between two previously described genetic sieve signatures (AA169, AA181). There was no correlation between the frequencies of CD4+ fine epitope responses and binding antibody.

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The figure shows the alleles present in any of the donors that responded to the specific epitope and the HLA binding prediction analysis.Accordingly, where possible, these algorithms were deployed to predict the binding of each recognized envelope peptide to the HLA class II alleles present in the corresponding responding individuals. Analysis of the resulting pattern of predicted binding was used in turn to infer HLA restriction.
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pone.0115582.g004: The figure shows the alleles present in any of the donors that responded to the specific epitope and the HLA binding prediction analysis.Accordingly, where possible, these algorithms were deployed to predict the binding of each recognized envelope peptide to the HLA class II alleles present in the corresponding responding individuals. Analysis of the resulting pattern of predicted binding was used in turn to infer HLA restriction.

Mentions: MHC class II restriction of the T cell lines was performed using a HLA class II restriction prediction analysis. The analysis is summarized in Fig. 4 and shows the parsed data by peptide recognition. DRB1*15:02 is strongly suggested to be a restricting allele for p16. Four of the five donors responding to the peptide carry this allele, which is predicted to bind with high affinity. The donor that did not have DRB1*15:02 had15:01, which has a binding characteristic similar to 15:02. However, it is possible that DRB3 or DQB1*05:01 could play a role too. All three donors responding to p31 expressed DRB1*12:02. As p31 is predicted to bind this allele with high affinity, suggesting that DRB1*12:02 is at least one restriction element for p31. DRB5*01 is similarly present in all three donors, and high binding is similarly predicted. A consistent pattern was more difficult to identify for p32. No allele is present in more than two of the four donors recognizing the peptide. At the same time, multiple DR and DQ alleles are predicted to bind the peptide with high affinity.


Identification of immunodominant CD4-restricted epitopes co-located with antibody binding sites in individuals vaccinated with ALVAC-HIV and AIDSVAX B/E.

Ratto-Kim S, de Souza MS, Currier JR, Karasavvas N, Sidney J, Rolland M, Valencia-Micolta A, Madnote S, Sette A, Nitayaphan S, Pitisuttuthum P, Kaewkungwal J, Rerks-Ngarm S, O'Connell R, Michael N, Robb ML, Marovich M, Kim JH - PLoS ONE (2015)

The figure shows the alleles present in any of the donors that responded to the specific epitope and the HLA binding prediction analysis.Accordingly, where possible, these algorithms were deployed to predict the binding of each recognized envelope peptide to the HLA class II alleles present in the corresponding responding individuals. Analysis of the resulting pattern of predicted binding was used in turn to infer HLA restriction.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4321833&req=5

pone.0115582.g004: The figure shows the alleles present in any of the donors that responded to the specific epitope and the HLA binding prediction analysis.Accordingly, where possible, these algorithms were deployed to predict the binding of each recognized envelope peptide to the HLA class II alleles present in the corresponding responding individuals. Analysis of the resulting pattern of predicted binding was used in turn to infer HLA restriction.
Mentions: MHC class II restriction of the T cell lines was performed using a HLA class II restriction prediction analysis. The analysis is summarized in Fig. 4 and shows the parsed data by peptide recognition. DRB1*15:02 is strongly suggested to be a restricting allele for p16. Four of the five donors responding to the peptide carry this allele, which is predicted to bind with high affinity. The donor that did not have DRB1*15:02 had15:01, which has a binding characteristic similar to 15:02. However, it is possible that DRB3 or DQB1*05:01 could play a role too. All three donors responding to p31 expressed DRB1*12:02. As p31 is predicted to bind this allele with high affinity, suggesting that DRB1*12:02 is at least one restriction element for p31. DRB5*01 is similarly present in all three donors, and high binding is similarly predicted. A consistent pattern was more difficult to identify for p32. No allele is present in more than two of the four donors recognizing the peptide. At the same time, multiple DR and DQ alleles are predicted to bind the peptide with high affinity.

Bottom Line: Non-transformed Env-specific T cell lines established from RV144 vaccinees were used to determine the fine epitope mapping of the V2 and C1 responses and the HLA class II restriction.Data showed that there are two CD4+ epitopes contained within the V2 loop: one encompassing the α4β7 integrin binding site (AA179-181) and the other nested between two previously described genetic sieve signatures (AA169, AA181).There was no correlation between the frequencies of CD4+ fine epitope responses and binding antibody.

View Article: PubMed Central - PubMed

Affiliation: United States Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, 20910, United States of America.

ABSTRACT
We performed fine epitope mapping of the CD4+ responses in the ALVAC-HIV-AIDSVAX B/E prime-boost regimen in the Thai Phase III trial (RV144). Non-transformed Env-specific T cell lines established from RV144 vaccinees were used to determine the fine epitope mapping of the V2 and C1 responses and the HLA class II restriction. Data showed that there are two CD4+ epitopes contained within the V2 loop: one encompassing the α4β7 integrin binding site (AA179-181) and the other nested between two previously described genetic sieve signatures (AA169, AA181). There was no correlation between the frequencies of CD4+ fine epitope responses and binding antibody.

Show MeSH