The peptide-binding specificity of HLA-A*3001 demonstrates membership of the HLA-A3 supertype

作者：Lamberth Kasper^*; Roder Gustav; Harndahl Mikkel; Nielsen Morten; Lundegaard Claus; Schafer Nielsen Claus; Lund Ole; Buus Soren

来源：Immunogenetics, 2008, 60(11): 633-643.

DOI：10.1007/s00251-008-0317-z

• Supertype
• HLA polymorphism
• HLA-I specificity
• Positional scanning combinatorial peptide library
• Peptide-HLA prediction

Human leukocyte antigen class I (HLA-I) molecules are highly polymorphic peptide receptors, which select and present endogenously derived peptide epitopes to CD8+ cytotoxic T cells (CTL). The specificity of the HLA-I system is an important component of the overall specificity of the CTL immune system. Unfortunately, the large and rapidly increasing number of known HLA-I molecules seriously complicates a comprehensive analysis of the specificities of the entire HLA-I system (as of June 2008, the international HLA registry holds > 1,650 unique HLA-I protein entries). In an attempt to reduce this complexity, it has been suggested to cluster the different HLA-I molecules into "supertypes" of largely overlapping peptide-binding specificities. Obviously, the HLA supertype concept is only valuable if membership can be assigned with reasonable accuracy. The supertype assignment of HLA-A*3001, a common HLA haplotype in populations of African descent, has variously been assigned to the A1, A3, or A24 supertypes. Using a biochemical HLA-A*3001 binding assay, and a large panel of nonamer peptides and peptide libraries, we here demonstrate that the specificity of HLA-A*3001 most closely resembles that of the HLA-A3 supertype. We discuss approaches to supertype assignment and underscore the importance of experimental verification.

• 出版日期2008-11