The genetic diversity across global population (Black, Caucasoid, oriental, Hispanic, mixed race, Pacific Islander, American Indian and Australian aboriginal) are other vital issues in personalized/population based medicine. The human leukocyte antigen (HLA) genes in human chromosome 6 are extensively studied across global population using genetic data and about a 2000 HLA alleles have been named so far at IMGT/HLA database. Extensive HLA polymorphism and peptide diversity are critical issues in HLA-peptide binding estimation for T-cell mediated immune response. The precise evaluation of HLA peptide binding finds application in epitope design for the development of vaccines and diagnostics of diseases associated with CD4+ (example, type 1 diabetes, malaria) and CD8+ (example, several viral infections) T-cellular immunity. HLA class II binding peptides have an extended conformation at the binding groove unlike class I. This increases peptide binding combinations of varying length at the groove having eventual effect in the host immune response to infectious agents. Discussion on the significance of prediction models to large HLA allele coverage representing sampled global population towards the development of diagnostics and vaccines will be presented.