• DECODE’s characterization of epitopes, T cell receptor (TCR) sequences and T cell phenotype provides new insights into the memory response to SARS-CoV-2 infection

CAMBRIDGE, Mass. – November 18, 2021 – Repertoire Immune Medicines, announced today that Science Immunology published the company’s research showing that human leukocyte antigen (HLA) genotype significantly influenced the immune recall of CD8+ T cells (cytotoxic T lymphocytes) in reaction to SARS-CoV-2 infection. The paper, “Allelic variation in Class I HLA determines CD8+ T cell repertoire shape and cross-reactive memory responses to SARS-CoV-2”, was published online today in Science Immunology.

“Our ability to develop optimal treatments for disease and vaccines for viral infections like COVID-19 requires that we fully understand the features of a successful immune response,” said Anthony Coyle, Ph.D., President, Research and Development, Repertoire Immune Medicines. “The association between specific HLA genotypes and the CD8+ T cell response we observed using our DECODE™ platform may have important implications for vaccine development to address long-term immunity and protection against variants.”

The cell-mediated immunity required to eliminate virally infected cells is facilitated by antigens presented by HLAs. When recognized by the immune system, the presented antigens can trigger long-term memory, allowing CD8+ T cells to respond quickly if a viral antigen appears again. However, viral variants with altered antigens can potentially circumvent T cell memory, rendering the immune response less effective. Therefore, a more complete understanding of the underlying cellular mechanisms that regulate immunity and contribute to long-term protection is required with infectious diseases like COVID-19.

To further define the cellular mechanisms involved in memory responses to SARS-CoV-2, Repertoire’s DECODE platform was utilized to provide a comprehensive decoding of CD8+ T cell response in 76 people across three cohorts: patients actively infected with SARS-CoV-2, patients who had recovered from infection, and individuals who had not been exposed to the virus.

“Using the DECODE platform, we were able to identify which epitopes were involved in the immune response to SARS-CoV-2 infection and the HLAs that drove cross-reactive memory, as seen in some people who had not been exposed to the virus,” said Daniel Pregibon, Ph.D., Head of Platform Discovery and Technology, Repertoire Immune Medicines. “While the extent of the protection from existing memory T cells would need to be further explored, we believe that understanding this aspect of response is key to the development of next generation T cell-based vaccines for COVID-19 and other infectious diseases.”

In this study, approximately 97 million CD8+ T cells from the 76 patients were interrogated using DECODE, which identified T cell specificity to 648 epitopes presented by four HLA alleles across the SARS-CoV-2 proteome. The study identified key epitopes recognized at high prevalence by the cellular response, characterized shared features of T cell receptor (TCR) sequences across patients, and explored T cell function at single-cell resolution.

DECODE identified a central memory phenotype and TCR cross-reactivity in individuals who had not been exposed to SARS-CoV-2 but who had past exposure to endemic common cold viruses with proteome sequences highly related to SARS-CoV-2, including beta coronavirus strains HKU1 and OC43. An association between specific HLA genotypes and the CD8+ T cell response to SARS-CoV-2 was also observed, which may have important implications for understanding elements of vaccine design that are likely to confer long-term immunity to protect against SARS-CoV-2 variants and related viral pathogens.

About the DECODE Platform

The DECODE platform is a powerful discovery engine that characterizes essential elements of the immune synapse. In particular, the platform identifies TCR-antigen pairs in the context of other important features of the immune synapse, such as T cell function and how these antigens are presented by molecules on antigen-presenting cells, known as major human leukocyte antigen, or HLA, molecules. We believe these insights into key factors that govern immune function in different diseases will enable us to design and develop novel immune product candidates.

About Repertoire Immune Medicines

Repertoire Immune Medicines is dedicated to creating treatments for diseases based on the power of the human T cell repertoire to eliminate cancer cells, target pathogens, and regulate immune function.

Repertoire’s strategy lies in understanding the immune synapse – the interaction between specific T cells and the corresponding antigen-presenting cells that dictate T cell activity. The company’s proprietary DECODE™ technology platform, developed by Repertoire scientists, provides a comprehensive understanding of the full repertoire of interactions between T cell receptors and their antigen targets. We believe the ability to decode these interactions represents one of the greatest opportunities for innovation in medical science.

Repertoire’s team of more than 150 operates from sites in Cambridge, Massachusetts, and Zurich, Switzerland, and uses its DECODE technology to rationally design treatments for cancers, autoimmune disorders, and infectious diseases.

To learn more about Repertoire Immune Medicines, please visit our website: www.repertoire.com and follow us on LinkedIn and Twitter.