Distribution of clusters of CTL epitopes in a representative non-membranal and membrane-spanning protein and alignment with transmembrane α-helices and loops.

<p>Sample plots of the topological map (generated by TMHMM predictions) of two representative proteins. Red segments represent the probability of having a helical region, while the thin blue and pink lines represent inside and outside loops, respectively. In the lower part of every protein chart, a bar represents a cluster of predicted epitopes. Co-localization of the putative MHC binders with the predicted helix or loop region in the protein is marked by a grey box. (A) A sample of a non-membranal protein (gi|89256893) carrying a cluster at density 0.8, harboring 23 putative epitopes, four of which are a responders. This represents the 18% non-membranal proteins carrying high density clusters (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0036440#pone-0036440-g004" target="_blank">Figure 4</a>). (B) A sample of a transmembrane protein (gi|89256946) carrying four clusters (clusters #1–4) within a α-helical transmembrane domain, (marked by “TM"), and an additional cluster (cluster #5) co-localized with an outside loop domain (marked by “loop") between two transmembranal regions. The total number of putative epitopes in clusters #1–4 is 102 and in cluster #5 is 17, which contain 3 and 2 responders, respectively. This sample protein provides an example for the high frequency of clusters in helical regions but also demonstrates the presence of high density clusters in loops (there are examples of other proteins, not shown, where clusters span both transmembrane and loop regions).