{Reference Type}: Journal Article
{Title}: Microbiota dictate T cell clonal selection to augment graft-versus-host disease after stem cell transplantation.
{Author}: Yeh AC;Koyama M;Waltner OG;Minnie SA;Boiko JR;Shabaneh TB;Takahashi S;Zhang P;Ensbey KS;Schmidt CR;Legg SRW;Sekiguchi T;Nelson E;Bhise SS;Stevens AR;Goodpaster T;Chakka S;Furlan SN;Markey KA;Bleakley ME;Elson CO;Bradley PH;Hill GR;
{Journal}: Immunity
{Volume}: 57
{Issue}: 7
{Year}: 2024 Jul 9
{Factor}: 43.474
{DOI}: 10.1016/j.immuni.2024.05.018
{Abstract}: Allogeneic T cell expansion is the primary determinant of graft-versus-host disease (GVHD), and current dogma dictates that this is driven by histocompatibility antigen disparities between donor and recipient. This paradigm represents a closed genetic system within which donor T cells interact with peptide-major histocompatibility complexes (MHCs), though clonal interrogation remains challenging due to the sparseness of the T cell repertoire. We developed a Bayesian model using donor and recipient T cell receptor (TCR) frequencies in murine stem cell transplant systems to define limited common expansion of T cell clones across genetically identical donor-recipient pairs. A subset of donor CD4+ T cell clonotypes differentially expanded in identical recipients and were microbiota dependent. Microbiota-specific T cells augmented GVHD lethality and could target microbial antigens presented by gastrointestinal epithelium during an alloreactive response. The microbiota serves as a source of cognate antigens that contribute to clonotypic T cell expansion and the induction of GVHD independent of donor-recipient genetics.