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

  • Gfeller D Department of Oncology, Ludwig Institute for Cancer Research, University of Lausanne, 1066 Epalinges, Switzerland; david.gfeller@unil.ch.
  • Guillaume P Department of Oncology, Ludwig Institute for Cancer Research, University of Lausanne, 1066 Epalinges, Switzerland.
  • Michaux J Department of Oncology, Ludwig Institute for Cancer Research, University of Lausanne, 1066 Epalinges, Switzerland.
  • Pak HS Department of Oncology, Ludwig Institute for Cancer Research, University of Lausanne, 1066 Epalinges, Switzerland.
  • Daniel RT Service of Neurosurgery, University Hospital of Lausanne, 1011 Lausanne, Switzerland.
  • Racle J Department of Oncology, Ludwig Institute for Cancer Research, University of Lausanne, 1066 Epalinges, Switzerland.
  • Coukos G Department of Oncology, Ludwig Institute for Cancer Research, University of Lausanne, 1066 Epalinges, Switzerland.
  • Bassani-Sternberg M Department of Oncology, Ludwig Institute for Cancer Research, University of Lausanne, 1066 Epalinges, Switzerland.
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  • 2018-11-16
Published in:
  • Journal of immunology (Baltimore, Md. : 1950). - 2018
Alleles
Antigen Presentation
Antigens
CD8-Positive T-Lymphocytes
Computational Biology
Epitopes, T-Lymphocyte
HLA Antigens
Histocompatibility Antigens Class I
Humans
Immunity, Cellular
Immunodominant Epitopes
Ligands
Meningioma
Models, Chemical
Peptides
Polymorphism, Genetic
Protein Binding
T-Cell Antigen Receptor Specificity
English 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.
Language
  • English
Open access status
bronze
Identifiers
Persistent URL
https://folia.unifr.ch/global/documents/246688
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