Antigen Processing in Autoimmunity and Cancer—Mechanisms and Translational Perspectives

A special issue of Cells (ISSN 2073-4409).

Deadline for manuscript submissions: 25 August 2026 | Viewed by 5046

Editor


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Guest Editor
Institut Necker-Enfants Malades INEM, Paris, France
Interests: autoimmunity; antigen presentation

Special Issue Information

Dear Colleagues,

Antigen processing refers to a series of molecular events that result in the presentation of antigenic peptides by major histocompatibility complex (MHC) molecules. These events include the cellular synthesis or uptake of protein antigens, their often-stepwise proteolytic degradation, the transport of peptides to sites of MHC complex assembly, chaperone-assisted MHC molecule loading with peptides, and the transport of MHC to the cell surface. Associations between human genetic polymorphisms and numerous autoimmune diseases, as well as anti-infectious immune responses, showcase the variable efficacy and susceptibility to modulation of the antigen processing machinery. This variation implicates polymorphism not only in MHC molecules but also in proteolytic enzymes, such as endoplasmic reticulum aminopeptidases (ERAPs). The importance of an unperturbed function of antigen processing for organismal homeostasis is highlighted by downregulation of key elements in this machinery by malignant or virally infected cells. Conversely, understanding of the impact of molecular players in antigen processing can be exploited to modulate immune responses, for example, by enhancing antitumor immunity or attenuating autoimmune responses.

This Special Issue will present a collection of original research articles and reviews that, on the one hand, report and discuss harmful interference with antigen processing and presentation in autoimmunity and cancer and, on the other hand,  present leads and approaches to exploiting and manipulating antigen processing to promote favorable enhancement of antitumor immunity and dampening of autoimmune responses.

Prof. Dr. Peter Van Endert
Guest Editor

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Keywords

  • major histocompatibility molecule
  • antigen processing
  • antigen presentation
  • protease
  • endoplasmic reticulum aminopeptidase
  • antitumor immunity
  • autoimmunity
  • immunotherapy

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Published Papers (2 papers)

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Review

36 pages, 1501 KB  
Review
Messing with Signal 1: How Perturbed MHC Class I Antigen Presentation Contributes to Cancer
by Myriam Lawand, Salman Al Rayess, Rawad Jaber and Peter van Endert
Cells 2026, 15(7), 653; https://doi.org/10.3390/cells15070653 - 7 Apr 2026
Viewed by 1878
Abstract
The antigen presentation machinery processes proteins for presentation to T cells, thereby controlling activation of the adaptive cellular immune response. Perturbation of this machinery has been linked to the development of various diseases. This review describes the function of the Major Histocompatibility Complex [...] Read more.
The antigen presentation machinery processes proteins for presentation to T cells, thereby controlling activation of the adaptive cellular immune response. Perturbation of this machinery has been linked to the development of various diseases. This review describes the function of the Major Histocompatibility Complex class I antigen presentation machinery and highlights how its perturbation can lead to compromised immune function and disease progression in the context of cancer. We categorize these perturbations into four distinct mechanistic levels: peptide generation, peptide loading, MHC class I integrity, and epigenetic regulation. This enables an integrated view of their functional impact on immune recognition, supporting therapeutic efforts to target antigen presentation or exploit these alterations in cancer. Full article
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17 pages, 580 KB  
Review
MHC Class II and Beyond: Complex Role of CD74 in Cancer
by Joanna Bandola-Simon and Paul A. Roche
Cells 2026, 15(2), 128; https://doi.org/10.3390/cells15020128 - 11 Jan 2026
Cited by 3 | Viewed by 2590
Abstract
Invariant chain, also known as CD74 when expressed on the plasma membrane, is classically recognized for its role in Major Histocompatibility Complex class II molecule assembly, trafficking, and peptide loading in professional antigen presenting cells. However, recent studies implicate CD74 as a broader [...] Read more.
Invariant chain, also known as CD74 when expressed on the plasma membrane, is classically recognized for its role in Major Histocompatibility Complex class II molecule assembly, trafficking, and peptide loading in professional antigen presenting cells. However, recent studies implicate CD74 as a broader regulator of tumor–immune interactions, modulating antigen presentation, cytokine signaling, and immune evasion across diverse cancers. This review synthesizes emerging evidence that CD74 functions as a “master regulator” of antigen presentation in cancer, integrating its canonical chaperone role with its noncanonical role in transcription regulation and in signaling via macrophage migration inhibitory factor. We explore how tumor microenvironmental contexts redefine CD74 biology, influencing antitumor immunity and therapeutic outcomes. Full article
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