Journal Article

Idiotope-Driven T-Cell/B-Cell Collaboration-Based T-Cell Epitope Prediction Using B-Cell Receptor Repertoire Sequences in Infectious Diseases

Moi, Meng Ling, Shiina, Takashi, Nakamura, Yukio, Suzuki, Ryuji, Shin-I, Tadasu

2023

Overview

T-cell recognition of antigen epitopes is a crucial step for the induction of adaptive immune responses, and the identification of such T-cell epitopes is, therefore, important for understanding diverse immune responses and controlling T-cell immunity. A number of bioinformatic tools exist that predict T-cell epitopes; however, many of these methods highly rely on evaluating conventional peptide presentation by major histocompatibility complex (MHC) molecules, but they ignore epitope sequences recognized by T-cell receptor (TCR). Immunogenic determinant idiotopes are present on the variable regions of immunoglobulin molecules expressed on and secreted by B-cells. In idiotope-driven T-cell/B-cell collaboration, B-cells present the idiotopes on MHC molecules for recognition by idiotope-specific T-cells. According to the idiotype network theory formulated by Niels Jerne, such idiotopes found on anti-idiotypic antibodies exhibit molecular mimicry of antigens. Here, by combining these concepts and defining the patterns of TCR-recognized epitope motifs (TREMs), we developed a T-cell epitope prediction method that identifies T-cell epitopes derived from antigen proteins by analyzing B-cell receptor (BCR) sequences. This method allowed us to identify T-cell epitopes that contain the same TREM patterns between BCR and viral antigen sequences in two different infectious diseases caused by dengue virus and SARS-CoV-2 infection. The identified epitopes were among the T-cell epitopes detected in previous studies, and T-cell stimulatory immunogenicity was confirmed. Thus, our data support this method as a powerful tool for the discovery of T-cell epitopes from BCR sequences.

• Publisher: MDPI AG,MDPI
• Subject: anti-idiotypic antibody / Antibodies / antigen / Antigen presentation / Antigenic determinants / Antigens / B cells / B-cell receptor / B-lymphocytes / bioinformatics / Cell receptors / Cell recognition / Cells / Collaboration / Communicable diseases / Coronaviruses / COVID-19 / Dengue fever / Dengue virus / Encephalitis / Epitopes / Epitopes, B-Lymphocyte / Epitopes, T-Lymphocyte / Genetic aspects / Genomes / Health aspects / Humans / idiotope-driven T-B collaboration / idiotype network / Immune response / Immunogenicity / immunoglobulins / Infectious diseases / Lymphocytes B / Lymphocytes T / Major histocompatibility complex / Medical research / Medicine, Experimental / Mimicry / molecular mimicry / network theory / Penicillin / Peptides / Physiological aspects / prediction / Receptors, Antigen, B-Cell / Receptors, Antigen, T-Cell / repertoire analysis / SARS-CoV-2 / Severe acute respiratory syndrome coronavirus 2 / T cell receptors / T cells / T-cell epitope / T-Lymphocytes / Tropical diseases / viral antigens / Viruses / West Nile virus