Department of
Biology

Dr. Mohindar Murugesh Karunakaran obtained his Master’s degree in Biotechnology from the University of Madras. He began his scientific career with a PhD in Molecular Immunology and Immunogenetics at the Institute of Virology and Immunobiology, University of Würzburg, Germany, under the supervision of Prof. Thomas Herrmann. During his doctoral and postdoctoral research, he extensively investigated human Vγ9Vδ2 T cells and the molecular mechanisms underlying their activation. In 2026, he joined IISER Pune as an Assistant Professor. His research focuses on understanding how human Vγ9Vδ2 T cells recognise and respond to stressed, infected, and cancerous cells, with particular emphasis on the immunomodulatory functions of butyrophilin (BTN) proteins in γδ T-cell activation and immune regulation.

Research

Research Themes

1. Molecular mechanisms of Vγ9Vδ2 TCR–Butyrophilin interactions
   How do BTN proteins assemble and communicate with the γδ T-cell receptor to trigger immune activation?
2. Comparative immunology: Human, alpaca, and camelid γδ T-cell biology
   What can evolution teach us about unconventional T-cell immunity across species?
3. Immunomodulatory functions of Butyrophilin proteins in infection and cancer
   How do BTN family members promote or suppress immune responses within diseased tissues?

Human Vγ9Vδ2 T cells are a unique population of immune cells with remarkable potential to combat cancer and infectious diseases. Our research seeks to understand the molecular mechanisms that govern how these cells recognize stressed tissues, initiate immune responses, and how these processes can be harnessed for therapeutic benefit. We investigate how butyrophilin (BTN) proteins assemble and communicate with the Vγ9Vδ2 T-cell receptor to regulate immune activation, and how alterations in these interactions influence immune responses in health and disease. To uncover the evolutionary principles underlying this unique recognition system, we employ comparative immunology using human and camelid models, providing insights that are difficult to obtain from conventional animal models. We also explore the immunomodulatory roles of BTN family members within the tumour microenvironment and during infection, where they can either promote or restrain immune responses. Our research integrates molecular and cellular immunology with protein engineering, advanced imaging, genome editing, and functional immune assays to bridge fundamental discoveries with translational applications. Through these complementary approaches, we aim to advance our understanding of unconventional T-cell biology and contribute to the development of next-generation immunotherapies.

Selected Publications

1. Karunakaran MM* et al., A distinct topology of BTN3A IgV and B30.2 domains controlled by juxtamembrane regions favors optimal human γδ T cell phosphoantigen sensing. Nat Commun 2023 Nov 22;14(1):7617. doi: 10.1038/s41467-023-41938-8.PMID: 37993425 (First and *co-corresponding author).
2. Fichtner AS, Karunakaran MM et al., Alpaca (Vicugna pacos), the first nonprimate species with a phosphoantigen-reactive Vγ9Vδ2 T cell subset. Proc Natl Acad Sci U S A. 2020 Mar 24;117(12):6697-6707. doi: 10.1073/pnas.1909474117. PMID: 32139608
3. Karunakaran MM# et al., Butyrophilin-2A1 Directly Binds Germline-Encoded Regions of the Vγ9Vδ2 TCR and Is Essential for Phosphoantigen Sensing. Immunity. 2020 Mar 17;52(3):487-498.e6. doi: 10.1016/j.immuni.2020.02.014. Epub 2020 Mar 9. PMID: 32155411. (# Shared First author)
4. Riaño F#, Karunakaran MM# et al., Vγ9Vδ2 TCR-activation by phosphorylated antigens requires butyrophilin 3 A1 (BTN3A1) and additional genes on human chromosome 6. Eur J Immunol. 2014 Sep;44(9):2571-6. doi: 10.1002/eji.201444712. Epub 2014 Jun 30. PMID: 24890657 (# equal contribution)
5. Karunakaran MM et al., Vγ9 and Vδ2 T cell antigen receptor genes and butyrophilin 3 (BTN3) emerged with placental mammals and are concomitantly preserved in selected species like alpaca (Vicugna pacos). Immunogenetics. 2014 Apr;66(4):243-54. doi: 10.1007/s00251-014-0763-8. Epub 2014 Feb 14. PMID: 2452634.