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The Role of Tregitopes in Antibody Maturation Unveiled by EpiVax

In a groundbreaking study published in Frontiers in Immunology, EpiVax, Inc. has illuminated the pivotal role of Tregitopes, a specific type of peptide, in the maturation of antibodies during immune responses. This research carries far-reaching implications for the development of therapeutic antibodies.

Antibodies, produced by B cells, undergo a continuous maturation process as they adapt to specific immune targets, such as viruses. The latest findings from EpiVax reveal that as these antibodies mature, there is a notable decrease in the levels of Tregitopes contained within them. This decrease is crucial because it allows B cells to expand and persist in response to immune challenges.

The study titled "Regulatory T Cell Epitope Content in Human Antibodies Decreases During Maturation" was conducted by Dr. Andres Gutierrez and Dr. Annie De Groot at EpiVax, utilizing existing human antibody sequence data. Dr. Gutierrez remarked, "This work provides significant insights into how antibodies evolve over time, not just in terms of affinity but also regarding their interactions with the immune system."

The discovery of Tregitopes in 2008 marked a significant turning point in understanding the function of regulatory T cells (Tregs) in both human and animal immunity. Tregitopes may partially explain the tolerogenic effects observed in intravenous immunoglobulin (IVIG) therapy. Notably, peptides that share similarities with Tregitopes have also been identified in various self-proteins.

Earlier analyses of human antibody repertoires indicated a decrease in T cell epitopes as antibodies matured, but they did not distinguish between the dynamics of regulatory T cell epitopes versus effector T cell epitopes. In their recent study, the EpiVax team examined antibody repertoires from four healthy human donors, assessing three subsets of T cell epitopes: validated Tregitopes, potentially tolerated T cell epitopes, and potentially effector T cell epitopes.

The results were striking: as antibodies matured and exhibited greater affinity for their respective antigens, the content of Tregitopes consistently decreased, while the levels of potentially effector T cell epitopes increased. This trend suggests that the depletion of Tregitopes is a fundamental characteristic of antibody evolution. Further validation of this observation was achieved through in vitro testing of certain natural and modified Tregitope sequences.

Dr. De Groot emphasized the relevance of this mechanism in context with immunity against pathogens, the development of autoimmune antibodies during autoimmune diseases, and the selection of therapeutic antibody candidates. She stated, "We are pleased to contribute to the literature on immune regulation and antibody design."

About EpiVax

EpiVax is a leader in preclinical immunogenicity assessment and sequence optimization for peptide therapies, biologics, and vaccines. Collaborating with recognized partners globally, EpiVax accelerates the risk assessment of immunogenicity, immune modulation, and rapid vaccine design.

For more information, please contact:
Sarah Moniz
Business Development Director
sarah@epivax.com