title: A framework to sub-type HLA supertypes.
abstract: The human leukocyte antigen (HLA) alleles are extremely polymorphic among ethnic population and the peptide binding specificity varies for different alleles in a combinatorial manner. However, it has been suggested that majority of alleles can be covered within few HLA supertypes, where different members of a supertype bind similar peptides, yet exhibiting distinct repertoires. Since the overlap between different members of a supertype appears to be extensive, it is crucial to develop a framework for grouping alleles into supertypes just from sequence information. In this report, we define sub supertypes, where members show functional overlap with identical repertoire, and describe a strategy to group HLA-A, B and C alleles into different categories of sub supertypes. The strategy grouped 47% of 295 A alleles, 44% of 540 B alleles and 35% of 156 C alleles to just 36, 71 and 18 groups, respectively. The grouping is moderately validated using available binding data. However, the validation is limited due to lack of binding data. Hence, the data presented in this article serve as a framework to test specific functional overlap between alleles. The grouping of HLA alleles into different categories of sub supertypes has profound use in the understanding of antigenic peptide selection, degeneration and discrimination during T-cell mediated immune response. A complete knowledge of this phenomenon finds utility in epitope design for the development of HLA based vaccines and immuno-therapeutics.
authors.affiliation: School of Mechanical and Production Engineering, Nanyang Technological University, Nanyang Centre for Supercomputing and Visualization, Singapore 639798. mpandjassarame@ntu.edu.sg <mpandjassarame@ntu.edu.sg>
authors.forename: Pandjassarame
authors.initials: P
authors.lastname: Kangueane
authors.forename: Meena Kishore
authors.initials: MK
authors.lastname: Sakharkar
authors.forename: Ganapathy
authors.initials: G
authors.lastname: Rajaseger
authors.forename: Subhashini
authors.initials: S
authors.lastname: Bolisetty
authors.forename: Balasubramanian
authors.initials: B
authors.lastname: Sivasekari
authors.forename: Bing
authors.initials: B
authors.lastname: Zhao
authors.forename: Manickam
authors.initials: M
authors.lastname: Ravichandran
authors.forename: Paul
authors.initials: P
authors.lastname: Shapshak
authors.forename: Subramanian
authors.initials: S
authors.lastname: Subbiah
mesh_terms: D000483:Alleles; D005838:Genotype; D006680:HLA Antigens / Q000737:chemistry*; D015234:HLA-A Antigens / Q000737:chemistry; D015235:HLA-B Antigens / Q000737:chemistry; D015236:HLA-C Antigens / Q000737:chemistry; D006650:Histocompatibility Testing / Q000379:methods*; D006801:Humans; D016130:Immunophenotyping / Q000379:methods*; D010455:Peptides / Q000737:chemistry; D011485:Protein Binding; D014612:Vaccines / Q000737:chemistry
chemical_list: D006680:HLA Antigens; D015234:HLA-A Antigens; D015235:HLA-B Antigens; D015236:HLA-C Antigens; D010455:Peptides; D014612:Vaccines