Major histocompatibility complex (MHC) molecules bind short peptides derived from antigens and present these peptides on the surface of antigen-presenting cells (APCs) for recognition by T-cell receptors (TCRs). T-cell epitopes, which are peptides that bind to MHC molecules and trigger an immune response, are important for the development of epitope-based vaccines. MHC genes in humans, which are termed human leucocyte antigens (HLAs), exhibit a high frequency of polymorphisms. HLA molecules could be clustered into supertypes based on the similarity of peptide binding grooves or peptide binding specificities. Peptides that bind to a given HLA class I molecule frequently bind to multiple HLA molecules belonging to the same supertype. These Promiscuous peptides in the context of HLA supertypes were mentioned as HLA supertype-specific binders, showing great potential for the development of vaccines with broad and unbiased coverage of the human population.