HCMV cross-reactivity potential of 77 SCT DRP from whole exome sequencing data using sliding window match analysis.

<p>HCMV cross-reactivity potential of 77 SCT DRP from whole exome sequencing data using sliding window match analysis.</p

Matrix depicting T cell clonal cross-reactivity between CMVp-HLA and mHA-HLA.

<p>*-indicates response of the alloreactive T cell clone to a viral pathogen peptide,bound to the same HLA as the mHA and vice versa. For example, TC₁ recognizes, mHA₁ HLA + CMVp₂HLA, TC_1CMV recognizes, mHA₁ HLA + CMVp₁ HLA, and so on.</p

CMV+GVHD cross reactivity potential.

<p>Patient-specific peak CMV peptide matches intersecting peak alloreactive peptides (IC50<500 nM) as a cross-reactivity potential stratified by donor type contained within each DRP alloreactive peptide library.</p

CMV- Human match analysis per DRP (IC50 <500 nM) by donor type according to continuous amino acid sequence homology (one standard deviation from the mean value).

<p>CMV- Human match analysis per DRP (IC50 <500 nM) by donor type according to continuous amino acid sequence homology (one standard deviation from the mean value).</p

Bioinformatic pipeline of the alloreactive peptide library comparison with the CMV proteome.

<p>A determination of the potential for Pro-GVHD DRP cross-reactivity upon CMV reactivation correlated with GVHD-tissue specific distribution of peptides & immunogenicity.</p

GVHD tissue-specific immunogenic CMV peptide matches, CMV reactivation before GVHD patients.

<p>Patient-specific process of cross comparison along with the source genes, IC50 values to indicate inverse binding affinity and GVHD organ specific tissue involvement. *Note: Twelve patients with CMV reactivation/infection before GVHD onset exhibited previously identified immunogenic CMV peptide matches with gene expression specific to the tissues affected by GVHD (above); The filter of immunogenicity provides a connection to T cell reactivity shown <i>in vitro</i> to the listed CMV genes in a separate patient population [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0178763#pone.0178763.ref036" target="_blank">36</a>]; Patient 79 with muscle/fascia GVHD showed no muscle-specific previously <i>known immunogenic</i> CMV peptide matches but still had three relevant CMV peptide matches expressed in the skeletal muscle (not shown); Tissues in parentheses were also affected by GVHD but without immunogenic matches/expression by patient; Patients 67 and 71 experienced <i>de novo</i> CMV infection; All 13 patients exhibited multiple CMV peptide matches with unknown immunogenicity.</p

Human-CMV short sequence homology in GVHD tissue specific peptide and gene distribution from GTEx analysis (n = 18).

<p>GVHD incidence denotes the specific organs affected in each patient; Peptides, lists the number of unique peptide-HLA complexes matched between human and CMV peptide library; the column, <i>Genes</i> lists the source genes for the aforementioned peptides; <i>GVHD tissue specific peptides</i> lists the number of peptides which bind HLA with an IC50 <500nM, and are expressed in tissues affected by GVHD; <i>GVHD tissue gene expression</i> denotes the number of genes expressed at an RPKM >10 corresponding to the GVHD tissue specific peptides. Note: *- All patients with an asterisk following their numeric representation experienced CMV reactivation prior to GVHD (except Patients 67 and 71, <i>de novo</i> CMV infected) and patients without an asterisk experienced GVHD prior to CMV reactivation. **- human peptides may have overlapping areas of homology yielding a higher number of matches. Immunogenic CMV genes in this context refer to the genes associated with HCMV ORF-specific CD8+ T memory cell responses measured in frequency among CMV seropositive patients previously [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0178763#pone.0178763.ref036" target="_blank">36</a>].</p

Matrix depicting the T cell clonal interaction with mHA-HLA.

<p>Matrix depicting the T cell clonal interaction with mHA-HLA.</p