Several viruses including human herpes viruses (HHVs), human polyomavirus JCV, and human papilloma virus (HPV) have been implicated in brain cancer, albeit inconsistently. Since human leukocyte antigen (HLA) is centrally involved in the human immune response to viruses and has been implicated in brain cancer, we evaluated in silico the immunogenicity between 69 Class I HLA alleles with epitopes of proteins of 9 HHVs, JCV, and HPV with respect to a population-based HLA-brain cancer profile. We found that immunogenicity varied widely across HLA alleles with HLA-C alleles exhibiting the highest immunogenicity, and that immunogenicity scores were negatively associated with the population-based HLA-brain cancer profile, particularly for JCV, HHV6A, HHV5, HHV3, HHV8, and HHV7. Consistent with the role of HLA in foreign antigen elimination, the findings suggest that viruses with proteins of high HLA immunogenicity are eliminated more effectively and, consequently, less likely to cause brain cancer; conversely, the absence of highly immunogenic HLA may allow the viral antigens to persist, contributing to cancer.
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