Employing proteomics in the study of antigen presentation: an update

ABSTRACT

Introduction: Our immune system discriminates self from non-self by examining the peptide cargo of human leukocyte antigen (HLA) molecules displayed on the cell surface. Successful recognition of HLA-bound non-self peptides can induce T cell responses leading to, for example, the destruction of infected cells. Today, largely due to advances in technology, we have an unprecedented capability to identify the nature of these presented peptides and unravel the true complexity of antigen presentation.

Areas covered: In addition to conventional linear peptides, HLA molecules also present post-translationally modified sequences comprising a wealth of chemical and structural modifications, including a novel class of noncontiguous spliced peptides. This review focuses on these emerging themes in antigen presentation and how mass spectrometry in particular has contributed to a new view of the antigenic landscape that is presented to the immune system.

Expert Commentary: Advances in the sensitivity of mass spectrometers and use of hybrid fragmentation technologies will provide more information-rich spectra of HLA bound peptides leading to more definitive identification of T cell epitopes. Coupled with improvements in sample preparation and new informatics workflows, studies will access novel classes of peptide antigen and allow interrogation of rare and clinically relevant samples.

KEYWORDS:

• antigen presentation
• immunopeptidomics
• PTM

Declaration of interest

A Purcell discloses Australian National Health and Medical Research Council (NHMRC) project grants (APP1085018 and APP1084283); Australian Research Council (ARC) project grant (DP150104503); NHMRC Principal Research Fellowship (APP 1,137,739). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This manuscript is not funded.