SHARK THYMUS EMPLOYS UNUSUAL ANTIGEN RECEPTORS AND IMMUNOGENETIC MECHANISMS
Mike Criscitiello, Texas A&M University
M.F. Criscitiello*1, J.A. Ott1, T.C. Deiss1 1Texas A&M University, Department of Veterinary Pathobiology, College Station TX, USA firstname.lastname@example.org
All jawed vertebrates appear to use the thymus for T cell development and shaping of the primary T cell repertoire. We study the immune system of the nurse shark as it represents the oldest class of animals with our immunoglobulin, T cell receptor (TCR), MHC and thymus based adaptive immunity. While much architecture and gene expression is conserved between shark and mammalian thymus, some interesting differences are emerging. While somatic hypermutation is generally considered a B cell phenomenon, shark thymocytes employ it to diversify some TCR chains, alpha to a significant degree. This appears concentrated at the cortico-medullary junction, begging questions of how positive and negative selection are influenced. TCR delta in sharks is capable of generating a few different forms. In addition to the canonical Vdelta repertoire there are doubly-rearranging NARTCR that have two V domains plus the delta C domain, and chimeric delta chains that use immunoglobulin heavy chain variable segments along with diversity and joining segments from delta to encode the variable domain. Some of these quirks of shark are also found in the T cell repertoires of other vertebrate groups, including mammals. We think the TCR immunogenetics of this shark model may offer insights into the genesis of the system and the plasticity available in engineering antigen receptor immunotherapeutics.