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Published on: March 8, 2012
HLA-B*27:05-specific cytotoxic T lymphocyte epitopes in Indian HIV type 1C
Jagadish Chandrabose Sundaramurthi1, V D Ramanathan, Luke Elizabeth Hanna
1Division of Biomedical Informatics, Department of Clinical Research, National Institute for Research in Tuberculosis (Formerly Tuberculosis Research Centre) (ICMR), Chennai, Tamil Nadu, India.
Abstract:
HLA-B*27:05 is one of the widely reported alleles associated with resistance to HIV, while HLA-A24, HLA-B7, HLA-B*07:02, HLA-B*35:01, HLA-B*53:01, and HLA-B40 are reported to be associated with susceptibility to HIV. Using a bioinformatics approach we attempted to predict potential HLA-B*27:05-specific HIV-1C epitopes that do not bind to susceptibility-associated HLA alleles based on our hypothesis that such epitopes have a greater probability of eliciting a protective immune response in the host. A consensus sequence was built for all proteins of Indian clade C virus. Epitopes specific to HLA-B*27:05 were predicted from the consensus sequence using two different bioinformatics methods to enhance the accuracy of the prediction. Epitopes that were also predicted to bind to any of the susceptibility-associated HLA alleles were excluded from the list. The short-listed epitopes were modeled using MODPROPEP to refine the prediction. Fourteen peptides were identified as epitopes by both sequence-based methods and were found to interact strongly with HLA-B*27:05 by molecular modeling studies. Five of the 14 epitopes were previously reported as immunogenic by other researchers, while the remaining nine are novel. The 14 epitopes have been repeatedly identified by three different methods indicating their potential as useful candidates for an effective HIV vaccine.
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