HLA-driven variability in human cytomegalovirus immune recognition: Epitope predictions from a kidney transplant Cohort

BACKGROUND: Human cytomegalovirus (HCMV) infection causes life-threatening complications in transplant recipients. Despite a seroprevalence exceeding 90% in Peru, the influence of HLA diversity on HCMV immune recognition remains unexplored in the South American region. We aimed to characterize the HLA allele distribution in a Peruvian cohort and evaluate its impact on the predicted HCMV antigen-presentation landscape. METHODS: HLA genotyping (loci A, B, C, DRB1, DQA1, DQB1) was performed in 562 kidney transplant candidates and related donors. Common allele groups (AF5%) were assigned 4-digit resolution proxies based on local prevalence. Linear T-cell epitopes from the immunodominant antigens 65 kDa phosphoprotein (pp65), Immediate early protein 1 (IE1), and Envelope glycoprotein B (gB) were predicted using high-performance algorithms. Allelic capacity to strongly bind antigenic peptides was quantified using the Predicted Strong Binder Density (PSBD). RESULTS: We identified 16 HLA-I and 10 HLA-II common allele groups; 92% of their 4-digit proxies are widely distributed in SAM, while C*15:12 emerged as a potentially endemic variant in Peru. Screening yielded 954 HLA-I candidate epitopes, including 169 that correspond to previously reported IEDB epitopes with potential for immunotherapy. PSBD analysis revealed distinct predicted antigen-presentation profiles across the common HLA variants identified. CONCLUSION: Our findings provide updated Peruvian HLA data and define regional HCMV antigen-presentation profiles based on predicted MHC-peptide binding affinity (PSBD). Further experimental validation of these high-confidence candidate epitopes and HLA-HCMV association studies will be necessary to determine their immunogenicity and potential utility for immune monitoring and future immunotherapeutic applications across South American populations.