Fusobacterium nucleatum (FN) is an opportunistic pathogen associated with several diseases, including periodontitis, cardiovascular disease, and colorectal cancer. Owing to genetic variation, FN strains may display distinct epitope profiles to the host immune system. Likewise, the human leukocyte antigen allele repertoire is highly polymorphic and varies across ethnic groups. This study examines how these variations influence immune recognition of FN among different ethnicities and evaluates the potential for autoimmune responses arising from cross‑reactivity with the FN proteome. A set of 140 experimentally verified epitopes and their variants was analyzed for binding affinities to major histocompatibility complex Class‑I and Class‑II molecules. Using the prevalence of these molecules across ethnicities and their affinity for FN epitopes, a new metric—pathogen detection capacity (PDC)—was formulated. PDC enabled comparison of FN recognition across populations. Additionally, the FN proteome was assessed for similarity to human epitopes implicated in autoimmune disorders. Results showed that European, South Asian, and Amerindian populations had a greater potential to detect FN, whereas Oceanian groups exhibited comparatively lower PDC values. Within super‑populations, ethnicities that migrated from their ancestral homelands displayed altered PDC profiles relative to non‑migrating groups. The analysis also identified four previously unreported FN peptide fragments with potential antigenic properties. Overall, this study provides a foundational framework for understanding FN immunogenicity and its variation across ethnicities. The findings highlight that disease pathophysiology can differ meaningfully among populations and that ethnicity‑specific medical strategies may contribute to improved therapeutic outcomes.