Figure 1.JanusMatrix separates the amino acid sequence of T cell epitopes into TCR-facing residues and HLA binding cleft-facing residues, and then compares the TCR face to other putative T cell epitopes. JanusMatrix defines cross-reactive T cell epitopes as those that have the same MHC allele restriction, the same or similar T cell-facing residues (epitope), and conserved binding of MHC-facing residues (agretope). The HLA-facing residues of the comparators are allowed to vary, as long as they still bind to the original HLA allele. Epitopes that are identical in terms of their TCR face and are equally able to bind to the identical HLA, but differ in sequence, are rapidly identified from a given database of genomic sequences. This enables large-scale comparisons between TCR-homologous T cell epitopes from the HG, the HM, and the HP.