TY - JOUR TI - Predicted high-affinity binding of Porphyromonas gingivalis peptides to 334 human leukocyte antigen (HLA) Class I and Class II molecules AU - James, Lisa M. AU - Sanders, Matthew AU - Georgopoulos, Apostolos P. PY - 2026 JO - Exploration of Immunology VL - 6 SP - 1003271 DO - 10.37349/ei.2026.1003271 UR - https://www.explorationpub.com/Journals/ei/Article/1003271 AB - Aim: To determine predicted binding affinities of peptides from Porphyromonas gingivalis (P. gingivalis) proteins and identify those binding with high-affinity to human leukocyte antigen (HLA) molecules. Methods: We evaluated in silico binding affinities of all possible linear 9-mer and 15-mer peptides of 13 P. gingivalis proteins with 334 HLA alleles; strong predicted binding affinity (IC50 < 50 nM) was considered a “hit”. Results: Predicted binding affinity of HLA molecules and P. gingivalis proteins varied substantially. We identified 798 unique 15-mer peptides that were predicted to bind strongly to Class II HLA molecules and did not overlap with any 15-mers of 83,607 human proteins and, thus, may be suitable candidates for P. gingivalis vaccine development. Conclusions: Individual differences in HLA shape the adaptive immune system response to P. gingivalis and other antigens via variability in binding affinity, a crucial first step in mounting immune system responses aimed at neutralization or elimination of non-self antigens, assuming host immunocompetency otherwise. Various preventive and therapeutic strategies aimed at reducing the burden of P. gingivalis are under investigation; the current findings document specific HLA-peptide combinations that may be a useful starting point for ongoing efforts toward P. gingivalis vaccine development. ER -