HLA class II immunopeptidomics reveals that co-inherited HLA-allotypes within an extended haplotype can improve proteome coverage for immunosurveillance

Proteomics. 2021 Sep;21(17-18):e2000160. doi: 10.1002/pmic.202000160. Epub 2021 Aug 17.

Abstract

Human leucocyte antigen (HLA) class II molecules in humans are encoded by three different loci, HLA-DR, -DQ, and -DP. These molecules share approximately 70% sequence similarity and all present peptide ligands to circulating T cells. While the peptide repertoires of numerous HLA-DR, -DQ, and -DP allotypes have been examined, there have been few reports on the combined repertoire of these co-inherited molecules expressed in a single cell as an extended HLA haplotype. Here we describe the endogenous peptide repertoire of a human B lymphoblastoid cell line (C1R) expressing the class II haplotype HLA-DR12/DQ7/DP4. We have identified 71350 unique naturally processed peptides presented collectively by HLA-DR12, HLA-DQ7, or HLA-DP4. The resulting "haplodome" is complemented by the cellular proteome defined by standard LC-MS/MS approaches. This large dataset has shed light on properties of these class II ligands especially the preference for membrane and extracellular source proteins. Our data also provides insights into the co-evolution of these conserved haplotypes of closely linked and co-inherited HLA molecules; which together increase sequence coverage of cellular proteins for immune surveillance with minimal overlap between each co-inherited HLA-class II allomorph.

Keywords: C1R; HLA class II; MHC; haplodome; immunopeptidomics; tissue typing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromatography, Liquid
  • HLA-DQ Antigens* / genetics
  • Haplotypes
  • Histocompatibility Antigens Class II
  • Humans
  • Monitoring, Immunologic
  • Proteome*
  • Tandem Mass Spectrometry

Substances

  • HLA-DQ Antigens
  • Histocompatibility Antigens Class II
  • Proteome