Potential of TCR sequencing in graft-versus-host disease

Abstract

Graft-versus-host disease (GvHD) remains one of the major complications following allogeneic haematopoietic stem cell transplantation (allo-HSCT). GvHD can occur in almost every tissue, with the skin, liver, and intestines being the mainly affected organs. T cells are implicated in initiating GvHD. T cells identify a broad range of antigens and mediate the immune response through receptors on their surfaces (T cell receptors, TCRs). The composition of TCRs within a T cell population defines the TCR repertoire of an individual, and this repertoire represents exposure to self and non-self proteins. Monitoring the changes in the TCR repertoire using TCR sequencing can provide an indication of the dynamics of a T cell population. Monitoring the frequency and specificities of specific TCR clonotypes longitudinally in different conditions and specimens (peripheral blood, GvHD-affected tissue samples) can provide insights into factors modulating immune reactions following allogeneic transplantation and will help to understand the underlying mechanisms mediating GvHD. This review provides insights into current studies of the TCR repertoire in GvHD and potential future clinical implications of TCR sequencing.

Expanding the repertoire reveals recurrent, cryptic, and hematopoietic HLA class I minor histocompatibility antigens

“…In these studies, however, data interpretation is complicated by limited sampling and information regarding antigen specificities or alloreactivity of the sequenced TCRs. 44 , 45 , 46 Koyama et al 46 showed that the majority of dominant TCRs found in GVHD-affected skin tissues were also detectable in blood, including the TCR of 1 of 2 confirmed alloreactive T-cell clones. However, Sacirbegovic et al 47 showed in mice that TCR repertoires in affected GVHD tissues compared with blood increasingly diverge in time because of T-cell influx from blood in early GVHD and subsequent maintenance by tissue-resident progenitor-like T cells in late GVHD.…”

New insights about immune populations in gastrointestinal GvHD

“…Because the TCR repertoire is highly dynamic in the early post-aHSCT setting as the immune system recovers, characterizing the TCR repertoire may allow prediction of clinical outcomes or toxicities. 10 Thus, a combination of these modalities could allow us to find new insights for understanding and managing GI-GvHD.…”