HLA A*24:02-restricted T cell receptors cross-recognize bacterial and preproinsulin peptides in type 1 diabetes.

CD8+ T cells destroy insulin-producing pancreatic β cells in type 1 diabetes through HLA class I-restricted presentation of self-antigens. Combinatorial peptide library screening was used to produce a preferred peptide recognition landscape for a patient-derived T cell receptor (TCR) that recognized the preproinsulin-derived (PPI-derived) peptide sequence LWMRLLPLL in the context of disease risk allele HLA A*24:02. Data were used to generate a strong superagonist peptide, enabling production of an autoimmune HLA A*24:02-peptide-TCR structure by crystal seeding.

Structure-guided engineering of immunotherapies targeting TRBC1 and TRBC2 in T cell malignancies.

Peripheral T cell lymphomas are typically aggressive with a poor prognosis. Unlike other hematologic malignancies, the lack of target antigens to discriminate healthy from malignant cells limits the efficacy of immunotherapeutic approaches. The T cell receptor expresses one of two highly homologous chains [T cell receptor β-chain constant (TRBC) domains 1 and 2] in a mutually exclusive manner, making it a promising target.

Health and social consequences for survivors of genocidal rape: A systematic scoping review.

The unique forms of trauma experienced by survivors of genocidal rape are not well understood. Hence, we conducted a systematic scoping review regarding the consequences for survivors of rape during genocide. Searches conducted in PubMed, Global Health, Scopus, PyscInfo, and Embase produced a total of 783 articles.

Unconventional modes of peptide-HLA-I presentation change the rules of TCR engagement.

The intracellular proteome of virtually every nucleated cell in the body is continuously presented at the cell surface the human leukocyte antigen class I (HLA-I) antigen processing pathway. This pathway classically involves proteasomal degradation of intracellular proteins into short peptides that can be presented by HLA-I molecules for interrogation by T-cell receptors (TCRs) expressed on the surface of CD8 T cells. During the initiation of a T-cell immune response, the TCR acts as the T cell's primary sensor, using flexible loops to mould around the surface of the pHLA-I molecule to identify foreign or dysregulated antigens.

GPU-Accelerated Discovery of Pathogen-Derived Molecular Mimics of a T-Cell Insulin Epitope.

The strong links between (Human Leukocyte Antigen) HLA, infection and autoimmunity combine to implicate T-cells as primary triggers of autoimmune disease (AD). T-cell crossreactivity between microbially-derived peptides and self-peptides has been shown to break tolerance and trigger AD in experimental animal models. Detailed examination of the potential for T-cell crossreactivity to trigger human AD will require means of predicting which peptides might be recognised by autoimmune T-cell receptors (TCRs).

Peptide cargo tunes a network of correlated motions in human leucocyte antigens.

Most biomolecular interactions are typically thought to increase the (local) rigidity of a complex, for example, in drug-target binding. However, detailed analysis of specific biomolecular complexes can reveal a more subtle interplay between binding and rigidity. Here, we focussed on the human leucocyte antigen (HLA), which plays a crucial role in the adaptive immune system by presenting peptides for recognition by the αβ T-cell receptor (TCR).

TCR-induced alteration of primary MHC peptide anchor residue.

The HLA-A*02:01-restricted decapeptide EAAGIGILTV, derived from melanoma antigen recognized by T-cells-1 (MART-1) protein, represents one of the best-studied tumor associated T-cell epitopes, but clinical results targeting this peptide have been disappointing. This limitation may reflect the dominance of the nonapeptide, AAGIGILTV, at the melanoma cell surface. The decapeptide and nonapeptide are presented in distinct conformations by HLA-A*02:01 and TCRs from clinically relevant T-cell clones recognize the nonapeptide poorly.