Identifying the HLA DRB1-DQB1 molecules and predicting epitopes associated with high-risk HPV infection clearance and redetection

• Published in: Scientific reports 2020-04, Vol.10 (1), p.7306, Article 7306
• Main Authors: Del Río-Ospina, Luisa, Camargo, Milena, Soto-De León, Sara C., Sánchez, Ricardo, Moreno-Pérez, Darwin A., Patarroyo, Manuel E., Patarroyo, Manuel A.
• Format: Article
• Language: English
• Subjects: 631/208/248; 631/67/1517; 692/499; Adult; Alleles; Alphapapillomavirus - genetics; Alphapapillomavirus - immunology; Disease-Free Survival; Drb1 protein; Epitopes; Epitopes - genetics; Epitopes - immunology; Female; Follow-Up Studies; Genetic diversity; Haplotypes; Histocompatibility antigen HLA; HLA-DQ beta-Chains - genetics; HLA-DQ beta-Chains - immunology; HLA-DRB1 Chains - genetics; HLA-DRB1 Chains - immunology; Human papillomavirus; Humanities and Social Sciences; Humans; Infections; Major histocompatibility complex; Middle Aged; multidisciplinary; Papillomavirus Infections - genetics; Papillomavirus Infections - immunology; Papillomavirus Infections - mortality; Peptides; Science; Science (multidisciplinary); Survival; Survival Rate; Tissue typing
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-020-64268-x

Several determining factors are involved in HPV infection outcomes; human leukocyte antigen (HLA) polymorphisms have been described as related factors. This study has ascertained the effect of genetic variation on HLA-DRB1 and DQB1 genes on HPV-16/-18/-31/-33/-45 and -58 clearance and redetection in Colombian women. PCR and qPCR were used for viral identification and the Illumina MiSeq system was used for HLA-typing of cervical samples (n = 276). Survival models were adjusted for identifying alleles/haplotypes related to HPV clearance/redetection; L1/L2 protein-epitope binding to MHC-II molecules was also predicted. Significant associations suggested effects favouring or hampering clearance/redetection events depending on the viral type involved in infection, e.g. just DRB1*12:01:01G favoured HPV-16 (coeff: 4.8) and HPV-45 clearance (coeff: 12.65) whilst HPV-18 (coeff: 2E-15), HPV-31 (coeff: 8E-17) and HPV-58 hindered elimination (coeff: 1E-14). An effect was only observed for some alelles when configured as haplotypes, e.g. DRB1*04:07:01G (having the greatest frequency in the target population) was associated with DQB1*02:01:1G or *03:02:03. Epitope prediction identified 23 clearance-related peptides and 29 were redetection-related; eight might have been related to HPV-16/-18 and -58 persistence and one to HPV-18 elimination. HLA allele/haplotype relationship with the course of HPV infection (clearance/redetection) depended on the infecting HPV type, in line with the specific viral epitopes displayed.