Determinants of tumor immune evasion: the role of T cell exposed motif frequency and mutant amino acid exposure.

Few neoepitopes detected in tumor biopsies are immunogenic. Tumor-specific T cell responses require both the presentation of an epitope that differs from wildtype and the presence of T cells with neoepitope-cognate receptors. We show that mutations detected in tumor biopsies result in an increased frequency of rare amino acid combinations compared to the human proteome and gastrointestinal microorganisms.

CD4 T Cells in the Blood of MS Patients Respond to Predicted Epitopes From B cell Receptors Found in Spinal Fluid.

B cells are important pathogenic players in multiple sclerosis (MS), but their exact role is not known. We have previously demonstrated that B cells from cerebrospinal fluid (CSF) of MS patients can activate T cells that specifically recognize antigenic determinants (idiotopes) from their B cell receptors (BCRs). The aim of this study was to evaluate whether prediction models could identify antigenic idiotopes of immunoglobulin heavy-chain variable (IGHV) transcriptomes in MS patients.

Immunoglobulin somatic hypermutation has clinical impact in DLBCL and potential implications for immune checkpoint blockade and neoantigen-based immunotherapies.

Background: Diffuse large B-cell lymphoma (DLBCL) harbors somatic hypermutation (SHM) in the immunoglobulin heavy chain and light chain variable region genes, IGHV and IGK/LV. Recent studies have revealed that IGV SHM creates neoantigens that activate T-cell responses against B-cell lymphoma.

Methods: To determine the clinical relevance of IGV SHM in DLBCL treated with standard immunochemotherapy, we performed next-generation sequencing of the immunoglobulin variable regions and complementarity determining region 3 (CDR3) for 378 patients with de novo DLBCL.

Human Cysteine Cathepsins Degrade Immunoglobulin G In Vitro in a Predictable Manner.

Cysteine cathepsins are critical components of the adaptive immune system involved in the generation of epitopes for presentation on human leukocyte antigen (HLA) molecules and have been implicated in degradation of autoantigens. Immunoglobulin variable regions with somatic mutations and random complementarity region 3 amino acid composition are inherently immunogenic. T cell reactivity towards immunoglobulin variable regions has been investigated in relation to specific diseases, as well as reactivity to therapeutic monoclonal antibodies.

A Role for Epitope Networking in Immunomodulation by Helminths.

Helminth infections, by nematodes, trematodes, or cestodes, can lead to the modulation of host immune responses. This allows long-duration parasite infections and also impacts responses to co-infections. Surface, secreted, excreted, and shed proteins are thought to play a major role in modulation.