TY - JOUR
T1 - The HLA Ligandome Comprises a Limited Repertoire of O-GlcNAcylated Antigens Preferentially Associated With HLA-B*07:02
AU - Mukherjee, Soumya
AU - Sanchez-Bernabeu, Alvaro
AU - Demmers, Laura C.
AU - Wu, Wei
AU - Heck, Albert J.R.
N1 - Funding Information:
We would like to acknowledge support for this research through the NWO funded Netherlands Proteomics Centre through the National Road Map for Large-scale Infrastructures program X-Omics (Project 184.034.019). LD and AH are further supported by the NWO Gravitation program Institute for Chemical Immunology (ICI00003). We acknowledge Dr. Stefan Stevanović (University of Tubingen, Germany) for providing the pan-HLA antibody W6/32.
Funding Information:
We would like to acknowledge support for this research through the NWO funded Netherlands Proteomics Centre through the National Road Map for Large-scale Infrastructures program X-Omics (Project 184.034.019). LD and AH are further supported by the NWO Gravitation program Institute for Chemical Immunology (ICI00003). We acknowledge Dr. Stefan Stevanovi? (University of Tubingen, Germany) for providing the pan-HLA antibody W6/32.
Publisher Copyright:
Copyright © 2021 Mukherjee, Sanchez-Bernabeu, Demmers, Wu and Heck.
PY - 2021/12/1
Y1 - 2021/12/1
N2 - Mass-spectrometry based immunopeptidomics has provided unprecedented insights into antigen presentation, not only charting an enormous ligandome of self-antigens, but also cancer neoantigens and peptide antigens harbouring post-translational modifications. Here we concentrate on the latter, focusing on the small subset of HLA Class I peptides (less than 1%) that has been observed to be post-translationally modified (PTM) by a O-linked N-acetylglucosamine (GlcNAc). Just like neoantigens these modified antigens may have specific immunomodulatory functions. Here we compiled from literature, and a new dataset originating from the JY B cell lymphoblastoid cell line, a concise albeit comprehensive list of O-GlcNAcylated HLA class I peptides. This cumulative list of O-GlcNAcylated HLA peptides were derived from normal and cancerous origin, as well as tissue specimen. Remarkably, the overlap in detected O-GlcNAcylated HLA peptides as well as their source proteins is strikingly high. Most of the O-GlcNAcylated HLA peptides originate from nuclear proteins, notably transcription factors. From this list, we extract that O-GlcNAcylated HLA Class I peptides are preferentially presented by the HLA-B*07:02 allele. This allele loads peptides with a Proline residue anchor at position 2, and features a binding groove that can accommodate well the recently proposed consensus sequence for O-GlcNAcylation, P(V/A/T/S)g(S/T), essentially explaining why HLA-B*07:02 is a favoured binding allele. The observations drawn from the compiled list, may assist in the prediction of novel O-GlcNAcylated HLA antigens, which will be best presented by patients harbouring HLA-B*07:02 or related alleles that use Proline as anchoring residue.
AB - Mass-spectrometry based immunopeptidomics has provided unprecedented insights into antigen presentation, not only charting an enormous ligandome of self-antigens, but also cancer neoantigens and peptide antigens harbouring post-translational modifications. Here we concentrate on the latter, focusing on the small subset of HLA Class I peptides (less than 1%) that has been observed to be post-translationally modified (PTM) by a O-linked N-acetylglucosamine (GlcNAc). Just like neoantigens these modified antigens may have specific immunomodulatory functions. Here we compiled from literature, and a new dataset originating from the JY B cell lymphoblastoid cell line, a concise albeit comprehensive list of O-GlcNAcylated HLA class I peptides. This cumulative list of O-GlcNAcylated HLA peptides were derived from normal and cancerous origin, as well as tissue specimen. Remarkably, the overlap in detected O-GlcNAcylated HLA peptides as well as their source proteins is strikingly high. Most of the O-GlcNAcylated HLA peptides originate from nuclear proteins, notably transcription factors. From this list, we extract that O-GlcNAcylated HLA Class I peptides are preferentially presented by the HLA-B*07:02 allele. This allele loads peptides with a Proline residue anchor at position 2, and features a binding groove that can accommodate well the recently proposed consensus sequence for O-GlcNAcylation, P(V/A/T/S)g(S/T), essentially explaining why HLA-B*07:02 is a favoured binding allele. The observations drawn from the compiled list, may assist in the prediction of novel O-GlcNAcylated HLA antigens, which will be best presented by patients harbouring HLA-B*07:02 or related alleles that use Proline as anchoring residue.
KW - HLA
KW - HLA-B07:02
KW - MHC
KW - O-GlcNAcylation modification
KW - immunopeptidome
KW - neo-antigen
UR - http://www.scopus.com/inward/record.url?scp=85121384174&partnerID=8YFLogxK
U2 - 10.3389/fimmu.2021.796584
DO - 10.3389/fimmu.2021.796584
M3 - Article
C2 - 34925382
AN - SCOPUS:85121384174
SN - 1664-3224
VL - 12
JO - Frontiers in Immunology
JF - Frontiers in Immunology
M1 - 796584
ER -