The soluble HLA immunopeptidome as active modulator and biomarker for T cell immunity in SARS-CoV-2 infection and COVID-19

• Applicant: Professorin Dr. Juliane Walz
• Subject Area: Immunology ; Clinical Infectiology and Tropical Medicine
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 543882037

The immune system rejects infected cells through recognition of human leucocyte antigen (HLA)-presented antigenic peptides and T cell-mediated cytotoxicity. However, antigen-specific T cell recognition and thus immune control of infectious disease, including SARS-CoV2 and COVID-19, shows high intra- and interindividual heterogeneity calling for biomarkers to determine T cell response, immunity and disease outcome. Whereas, huge effort has been made in recent years to characterize membrane-bound HLA molecules and their peptides to understand T cell immunity and identify novel antigen targets, much less attention was given to their secretion as soluble HLA molecules (sHLA) into body fluids. sHLA molecules, for which altered levels were reported in infectious and malignant disease, still carry their antigenic peptides (sIPep). I hypothesize that these peptides (i) are central for T cell-based immunity in SARS-CoV2, (ii) provide novel biomarkers for disease outcome and (iii) guide the development of novel therapeutic and preventive measures for COVID-19. To validate this hypothesis, I will provide a comprehensive analysis of sHLA levels, the sIPep, related T cell responses and their association with disease-related variables in large cohorts of healthy volunteers and COVID-19 patients and convalescents, using our unique expertise in mass spectrometry-based immunopeptidomics and high-throughput characterization of antigen-specific T cell response. This project opens new avenues in T cell immunity research with, in case of success, large impact on diagnostic, outcome prediction, vaccine design and drug development for SARS-CoV2.

• DFG Programme: Research Grants