Identification of elusive molecule from Dialysable leukocyte extracts mediating passive cellular immunity and their potential therapeutic utility

Authors

• PP Chaudhary
• M Yadav
• IA Myles

Abstract

Dialysable leukocyte extracts (DLE) are complexes in immunology comprised of low molecular weight substances. These fractions showed immunomodulatory properties which are primarily attributed to small peptides/or active molecule referred as “transfer factor” (TF). When collected from the breasts milk and peripheral blood, DLE was reported to confer immune reactivity and therapeutic benefit to from immune donors to naïve recipients. In the previous studies we elucidated that DLE activity is TCR beta dependent and antigen presenting cells (APCs)were the cellular target of DLE. DLE is made by antigen-specific effector memory CD8+ T cells, induces IL-6 from antigen-matched APCs, and ultimately elicits IL-17 from tissue-resident, bystander effector memory CD8+ T cells. However, to date, the molecular characterization and mechanistic understanding of DLE activity remains unclear. Using a combination of mass spectrometry and RNA sequencing approaches, our results aligned with the earlier studies reported stating the RNA nature of the TF. We identified DLE is comprised of a combination of the TCR beta CDR3 region (conferring antigen specificity) along with a non-coding RNA element. Ongoing work will synthesize each portion of the molecule in an attempt to clone to active compound to assess if passive cellular immunity through DLE could be a viable novel, therapeutic class.

Scientific Focus Area: Microbiology and Infectious Diseases

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