Structural Immunology

NON-COMMUNICABLE DISEASES / Immunology

Research Interests

Structural biology of immune recognition, molecular mimicry and allergy

Description of Research

Understanding the physiological processes of self-nonself discrimination in terms of physicochemical principles of molecular interactions has been a major focus of our research. Our work on the pluripotency of primary immune response led to discovering new ways of antibody degeneracy and has impacted the evolving paradigm shift in immune recognition and generation of antibody repertoire. We have analyzed how the immune system reacts when encountered with the antigens that keep changing shape and showed that the restricted paratope conformational repertoire on binding of an antigen to multiple independent antibodies may be relevant for minimizing possibility of selfreactive antibodies. Molecular insights into the functional mimicry in the context of immune response were addressed using structural, immunological and thermodynamic approaches. We have demonstrated how paratope plasticity facilitates molecular mimicry of otherwise unrelated antigens. While our analyses of carbohydrate-peptide mimicry provided important conceptual leads towards design and development of new generation of vaccines, the analyses involving carbohydrate-porphyrin mimicry provided possible mechanistic understanding of the molecular pathology of porphyria. Structural issues pertaining to innate immunity and food allergies are also being addressed.

The Group has recently developed an in-silico analysis to understand the structural changes in TCR variable regions during tumour antigen recognition. Large-scale parallel MD simulation studies were carried out on comprehensive datasets of antigen-free and antigen-bound TCRs (wild-type and mutant), using a scalable MD code on high-performance computing platforms. (Tripathi et al, 2021, J Biomol Struct Dyn 2021). The Group has been engaged in a major multi-institutional programme to carry out proteomic analysis associated with term and preterm birth with the aim of identifying possible predictive biomarkers. Identification of several up/down regulated proteins has provided interesting insights into the dynamics of protein expression during this process (Kumar et al, J Proteome Research, 2021).

Recent Publications