MHC articles from across Nature Portfolio

Human leukocyte antigen (HLA) class I peptide ligands (HLAIps) are targets for developing vaccines and immunotherapies. Here the authors report Thunder-DDA-PASEF, an immunopeptidomics method which enhances the identification of vital HLAIps crucial for vaccine and immunotherapy development.

Podoconiosis is triggered by long term barefoot exposure to volcanic red clay soil. Here, Negash et al characterise the immune profile of podoconiosis patients to show this disease is associated with high levels of immune activation and inflammation.

This study aims to build trust in MHC class I predictors by providing human-interpretable explanations. The explanations were assessed for accuracy, consistency across prediction models, and stability with similar peptides.

HLA-I plays a key role in triggering an immune response and predicting immune checkpoint efficacy. Here the authors develop a method for quantifying HLA-I neoantigen presentation capacity by integrating HLA-I allele divergence and neoantigens numbers, termed HAPS, to describe how immune checkpoint response may be mediated by HLA.

Bead-based assays to assess the donor-specific antibody profile of solid organ transplant patients often produce discordant results relative to cell-based alternatives. In this study, the authors demonstrate that, for some MHC class-II-specific antibodies, discordance can be attributed to recognition of the MHC class-I-derived peptides bound to MHC class-II molecules.

Radiation induced gastrointestinal syndrome is a complication of radiotherapy and the tumor suppressor p53 is implicated in protection from gastrointestinal toxicity. Here Wang and colleagues show that p53 protection against radiation-induced gastrointestinal syndrome involves intestinal stem cell function and inhibition of inflammation triggered by radiation via the IL12- p40/MHC-II axis.

The development of immunotherapies for acute myeloid leukemia (AML) has been limited by a lack of known tumor-specific targets. A study now shows the feasibility of developing highly sensitive and selective T cell-receptor-based therapies against an HLA-A*02:01-associated peptide derived from a recurrent mutation in a subset of patients with AML.

Individuals with the HLA-B*15:01 allele may have pre-existing T cells derived from seasonal coronavirus infections that cross-protect against SARS-CoV-2.

Antigen presentation is fundamental to anti-tumor immunity, but our understanding of the physiological and molecular inputs to the process in different contexts remains limited. Two new studies explore the contribution of cell-intrinsic proteolytic mechanisms and cell-extrinsic hot and cold tumor microenvironments in shaping the antigenic landscape in lung cancer.

A new study explores the links between diet and colorectal cancer risk by showing that changes to the intestinal microbiome in mice fed a high-fat diet result in attenuated MHC class II expression by intestinal stem cells and hence impaired immune surveillance of tumour initiation.