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. 2018 Dec 15;201(12):3705-3716.
doi: 10.4049/jimmunol.1800914. Epub 2018 Nov 14.

The Length Distribution and Multiple Specificity of Naturally Presented HLA-I Ligands

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The Length Distribution and Multiple Specificity of Naturally Presented HLA-I Ligands

David Gfeller et al. J Immunol. .
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Abstract

HLA-I molecules bind short peptides and present them for recognition by CD8+ T cells. The length of HLA-I ligands typically ranges from 8 to 12 aa, but variability is observed across different HLA-I alleles. In this study we collected recent in-depth HLA peptidomics data, including 12 newly generated HLA peptidomes (31,896 unique peptides) from human meningioma samples, to analyze the peptide length distribution and multiple specificity across 84 different HLA-I alleles. We observed a clear clustering of HLA-I alleles with distinct peptide length distributions, which enabled us to study the structural basis of peptide length distributions and predict peptide length distributions from HLA-I sequences. We further identified multiple specificity in several HLA-I molecules and validated these observations with binding assays. Explicitly modeling peptide length distribution and multiple specificity improved predictions of naturally presented HLA-I ligands, as demonstrated in an independent benchmarking based on the new human meningioma samples.

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