Abstract
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.
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Abbreviations
- PSCPL:
-
positional scanning combinatorial peptide libraries
- AP:
-
anchor position
- RB:
-
relative binding
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Acknowledgements
This work was supported by grants from the National Institutes of Health (grant HHSN266200400025C) and from the sixth framework program of the European Commission (grants LSHB-CT-2003-503231).
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After submission of this study, Sidney et al. have published a PSCPL analysis of HLA-A*3001 finding a similar peptide-binding motif as in this study (Sidney J, Assarsson E, Moore C, Ngo S, Pinilla C, Sette A, Peters B. “Quantitative peptide-binding motifs for 19 human and mouse MHC class I molecules derived using positional scanning combinatorial peptide libraries.” Immunome Res. 2008 Jan 25; 4:2) and concluded in another study that the HLA-A*3001 peptide-binding repertoire overlapped the A1 and A3 supertype (Sidney J, Peters B, Frahm N, Brander C, Sette A. “HLA class I supertypes: a revised and updated classification.” BMC Immunol. 2008 Jan 22; 9:1).
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Lamberth, K., Røder, G., Harndahl, M. et al. The peptide-binding specificity of HLA-A*3001 demonstrates membership of the HLA-A3 supertype. Immunogenetics 60, 633–643 (2008). https://doi.org/10.1007/s00251-008-0317-z
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DOI: https://doi.org/10.1007/s00251-008-0317-z