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Referee Comments: Referee 2

Posted by PLOS_ONE_Group on 21 Mar 2008 at 17:02 GMT

Referee 2's Review:

By mining the public data base, Frankild and colleagues developed a TCR peptide recognition mathematical model to predicte cross-reactivity of HIV epitope SLVNATVATL as well as other CTL epitopes. They found that peptide sequence similarity predicts CTL cross-reactivity, and that foreign antigens that are similar to self antigens are usually not immunogenic.

Although the bioinformatic excise is somewhat interesting, the results presented confirm what could be expected based on the existing experimental immunological data. The study design is not as clear as it could be. For example, there is no apparent rationale explaining why half of the paper focuses on Gag epitope SLVNATVATL (Fig. 1 and 2) and a quarter of the paper examines Nef CTL responses (Fig.4). Moreover, there is no experimental validation of any specific prediction made by the model.

On a minor note, attentions should be paid to the following details:

1) Reference 38 in Table 1 is nowhere to be found in the paper which cited 35 references.
2) References 36 and 37 are nowhere to be found, and reference 12 is misquoted as reference 13 in Figure 1.
3) In Figure 2, the phase "for three CTL clones G10, T4 and PBMC" needs to be revised since PBMC is not a clone.
4) In the results section, the estimated ligands for various T cell clones are misprinted as "5.6105, 3.2106, and 4.8106" instead of correct numbers of 5.6x105, 3.2x106, and 4.8x106.
5) It would be helpful to paginated the manuscript.

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N.B. These are the comments made by the referee when reviewing an earlier version of this paper. Prior to publication the manuscript has been revised in light of these comments and to address other editorial requirements.