Structural studies on antigen presentation in cancer and type 1 diabetes

The intricate interactions between T-cell receptors (TCRs) and major histocompatibility complexes (MHCs) are fundamental to the adaptive immune response, playing a crucial role in recognizing and responding to pathological states such as cancer and diabetes. Structural characterization of these interactions via X-ray crystallography provides profound insights into the molecular mechanisms underlying TCR-MHC recognition and specificity. This study focuses on elucidating the structural basis of TCR-MHC interactions within the contexts of oncological and autoimmune pathologies, specifically cancer and type 1 diabetes mellitus (T1DM). High-resolution X-ray crystallographic analyses reveal the conformational adaptations and binding affinities of TCRs to MHC-peptide complexes derived from tumor-associated antigens and pancreatic beta-cell autoantigens. These detailed structural insights enhance our understanding of TCR specificity and cross-reactivity, offering valuable perspectives on immune evasion in tumors and autoimmune destruction in diabetes. Thus, the findings have significant implications for the development of targeted immunotherapies and precision medicine approaches for both cancer and diabetes. The access to synchrotron radiation such as Xaloc and Xaira beamlines are critical to face these challenges. In the past calls, we have successfully harnessed these capabilities, and solved multiple proteins and complexes. We seek to continue this fruitful collaborations.