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Peer-reviewedCC BY 4.0PLOS One

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

7 affiliations
  1. 1Facultad de Ciencias Biológicas, Universidad Nacional Mayor de San Marcos, Av. Carlos Germán Amezaga, Lima, Peru
  2. 2Pathogen Genetics Research Group (PATHO-GEN), Organization for Medical Innovation and Collaboration for Sciences (OMICS), Lima, Peru
  3. 3Immunology and Cancer Research Group (IMMUCA), Organization for Medical Innovation and Collaboration for Sciences (OMICS), Lima, Peru
  4. 4Facultad de Medicina Humana, Universidad Católica de Santa María, Arequipa, Peru
  5. 5Área de Histocompatibilidad y Biología Molecular, Hospital Nacional Carlos Alberto Seguin Escobedo, Red Asistencial Arequipa, Seguro Social de Salud (EsSalud), Arequipa, Peru
  6. 6Facultad de Medicina, Universidad Nacional Mayor de San Marcos, Lima, Peru
  7. 7Escuela de Postgrado, Universidad Católica de Santa María, Arequipa, Peru

Abstract

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.

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BibTeX
@article{rosado2026hladriven,
  title = {{HLA-driven variability in human cytomegalovirus immune recognition: Epitope predictions from a kidney transplant Cohort}},
  author = {Mirella Dara Moreno Rosado and Tatiana Chavez-Arias and Obert Marín-Sánchez and Ricardo J. Juarez Zevallos and Alexis Germán Murillo Carrasco and César A. Ortiz Rojas and Yuma Ita-Balta and Ruy Diego Chacón Villanueva},
  journal = {PLOS One},
  year = {2026},
  month = oct,
  doi = {10.1371/journal.pone.0360632},
  url = {https://doi.org/10.1371/journal.pone.0360632},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - HLA-driven variability in human cytomegalovirus immune recognition: Epitope predictions from a kidney transplant Cohort
AU  - Mirella Dara Moreno Rosado
AU  - Tatiana Chavez-Arias
AU  - Obert Marín-Sánchez
AU  - Ricardo J. Juarez Zevallos
AU  - Alexis Germán Murillo Carrasco
AU  - César A. Ortiz Rojas
AU  - Yuma Ita-Balta
AU  - Ruy Diego Chacón Villanueva
PY  - 2026
DA  - 2026/10/15
JO  - PLOS One
DO  - 10.1371/journal.pone.0360632
UR  - https://doi.org/10.1371/journal.pone.0360632
AB  - 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.
SN  - 1932-6203
ER  -