Challenges and opportunities in analyzing and modeling peptide presentation by HLA-II proteins

Hesham ElAbd; Petra Bacher; Andreas Tholey; Tobias L Lenz; Andre Franke

doi:10.3389/fimmu.2023.1107266

Challenges and opportunities in analyzing and modeling peptide presentation by HLA-II proteins

Front Immunol. 2023 Mar 29:14:1107266. doi: 10.3389/fimmu.2023.1107266. eCollection 2023.

Authors

Hesham ElAbd¹, Petra Bacher^{1

2}, Andreas Tholey³, Tobias L Lenz⁴, Andre Franke¹

Affiliations

¹ Institute of Clinical Molecular Biology, University of Kiel, Kiel, Germany.
² Institute of Immunology, University of Kiel, Kiel, Germany.
³ Proteomics & Bioanalytics, Institute for Experimental Medicine, University of Kiel, Kiel, Germany.
⁴ Research Unit for Evolutionary Immunogenomics, Department of Biology, University of Hamburg, Hamburg, Germany.

Abstract

The human leukocyte antigen (HLA) proteins are an indispensable component of adaptive immunity because of their role in presenting self and foreign peptides to T cells. Further, many complex diseases are associated with genetic variation in the HLA region, implying an important role for specific HLA-presented peptides in the etiology of these diseases. Identifying the specific set of peptides presented by an individual's HLA proteins in vivo, as a whole being referred to as the immunopeptidome, has therefore gathered increasing attention for different reasons. For example, identifying neoepitopes for cancer immunotherapy, vaccine development against infectious pathogens, or elucidating the role of HLA in autoimmunity. Despite the tremendous progress made during the last decade in these areas, several questions remain unanswered. In this perspective, we highlight five remaining key challenges in the analysis of peptide presentation and T cell immunogenicity and discuss potential solutions to these problems. We believe that addressing these questions would not only improve our understanding of disease etiology but will also have a direct translational impact in terms of engineering better vaccines and in developing more potent immunotherapies.

Keywords: HLA-II & autoimmunity; TCR - T cell receptor; immunogenicitiy; immunotherapy; mass-spectrometry (MS) based immunopeptidomics; neoantigen.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

HLA Antigens*
Histocompatibility Antigens Class I*
Histocompatibility Antigens Class II / metabolism
Humans
Peptides
T-Lymphocytes

Substances

Histocompatibility Antigens Class I
HLA Antigens
Peptides
Histocompatibility Antigens Class II

Grants and funding

The manuscript was funded by the German Research Foundation DFG Research Unit 5042: miTarget—miTarget—The Microbiome as a Therapeutic Target in Inflammatory Bowel Diseases along with funding from the Cluster of Excellence 2167 “Precision Medicine in Chronic Inflammation (PMI)”. TL was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) – 437857095. The funding agencies had no role in the design, collection, analysis, and interpretation of data and neither in writing the manuscript.