We report three interesting cases concerning antibody-mediated rejection (AMR), associated or not with anti-donor-specific antibodies, and detection of implicated molecular epitopes. The first report presents a case of intra-allele sensitization. The second case presents an interesting case concerning Luminex mean fluorescence intensity (MFI) levels considered to be low risk antibodies (<1000), but producing AMR. The third case occurred after a second kidney transplantation mediated by antibodies directed against HLA-C antigens (MFI<1000) in the previous transplantation (which was considered to be an indicator of low-risk of AMR).
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Nat Commun
January 2025
Université Paris Cité, Institut Cochin, CNRS, INSERM, Paris, France.
Interferon (IFN)-α is the earliest cytokine signature observed in individuals at risk for type 1 diabetes (T1D), but the effect of IFN-α on the antigen repertoire of HLA Class I (HLA-I) in pancreatic β-cells is unknown. Here we characterize the HLA-I antigen presentation in resting and IFN-α-exposed β-cells and find that IFN-α increases HLA-I expression and expands peptide repertoire to those derived from alternative mRNA splicing, protein cis-splicing and post-translational modifications. While the resting β-cell immunopeptidome is dominated by HLA-A-restricted peptides, IFN-α largely favors HLA-B and only marginally upregulates HLA-A, translating into increased HLA-B-restricted peptide presentation and activation of HLA-B-restricted CD8 T cells.
View Article and Find Full Text PDFCurr Pharm Biotechnol
January 2025
Center for Vaccine Innovation, La Jolla Institute for Immunology (LJI), La Jolla, CA 92037, USA.
The SARS-CoV-2 pandemic has highlighted the need for society, as a whole, to be prepared against potential pandemics caused by a variety of different viral families of concern. Here, we describe a roadmap towards the identification and validation of conserved T cell epitope regions from Viral Families of Pandemic Potential (VFPP). For each viral family, we select a prototype virus, the sequence of which could be utilized in epitope identification screens.
View Article and Find Full Text PDFJ Transl Med
January 2025
Department of Breast and Thyroid Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China.
Background: T cell receptor (TCR)-engineered T cells targeting neoantigens originated from mutations in KRAS gene have demonstrated promising outcomes in clinical trials against solid tumors. However, the challenge lies in developing tumor-specific TCRs that avoid cross-reactivity with self-antigens to minimize the possibility of severe clinical toxicities. Current research efforts have been put towards strategies to eliminate TCR off-target recognition.
View Article and Find Full Text PDFEBioMedicine
January 2025
State Key Laboratory of Molecular Oncology, CAMS Key Laboratory of Translational Research on Lung Cancer, Department of Medical Oncology, National Cancer Centre/National Clinical Research Centre for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences Peking Union Medical College, Beijing, 100021, China. Electronic address:
Background: Small cell lung cancer (SCLC) represents a highly aggressive neuroendocrine tumour with a dismal prognosis. Currently, the identification of a specific tumour antigen that can facilitate immune-based therapies for SCLC remains elusive.
Methods: We employed liquid chromatography-tandem mass spectrometry (LC-MS/MS) to analyse cancer/testis antigens (CTAs) in SCLC cell lines and human tumour specimens.
Int J Mol Sci
December 2024
Department of Medicine, Division of Clinical Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto 14049-900, SP, Brazil.
Citrullination, a post-translational modification (PTM), plays a critical role in rheumatoid arthritis (RA) by triggering immune responses to citrullinated self-antigens. Some HLA-DRB1 genes encode molecules with the shared epitope (QKRAA/QRRAA) sequence in the peptide-binding groove which preferentially presents citrulline-modified peptides, like vimentin, that intensifies the immune response in RA. In this study, we used computational approaches to evaluate intermolecular interactions between vimentin peptide-ligands (with/without PTM) and HLA-DRB1 alleles associated with a significantly increased risk for RA development.
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