Repertoire of the αβ T‐cell receptor in the intestine

Abstract

The majority of T cells in the human and mouse intestine express the T-cell receptor (TCR) as an alphabeta heterodimer on their cell surface. As the major recognition element of antigens in the context of major histocompatibility complex-derived proteins, an examination of the structure of the alpha beta TCR in intestines has provided significant insights into the potential function of these cells and the major determinants that drive their selection. Studies in the human intestine have shown that the repertoires of intraepithelial lymphocytes (IELs), and likely lamina propria lymphocytes, are polyclonal before and shortly after birth, with the repertoire becoming oligoclonal in adults. Similarly, in adult mice the repertoire is oligoclonal, while in the newborn it is polyclonal. Investigations in mice have shown that some T cells may evade thymic selection. The population size and oligoclonality of IELs is influenced by the microbial content of the luminal microenvironment. This microenvironment probably directly determines the TCR repertoire. Studies in human inflammatory bowel disease (IBD) indicate that inflammation further skews the TCR repertoire. We speculate that dominant antigens associated with the pathogenesis of IBD are responsible for such skewing and that identifying the antigenic drivers may shed light on the environmental factors that trigger or potentiate human IBD.

Parallel T-cell cloning and deep sequencing of human MAIT cells reveal stable oligoclonal TCRβ repertoire

“…The same issue applies to invariant NKT and MAIT cells, which are restricted to nonpolymorphic antigen-presenting molecules and recognize evolutionarily conserved antigens. Oligoclonality is a hallmark of the T-cell populations resident in epithelia and the intestine 23,35,36 , and a skewed peripheral T-cell repertoire is present in chronic infections [37][38][39] , autoimmune diseases 40,41 and cancer [42][43][44] .…”

IL-2 receptor γ-chain molecule is critical for intestinal T-cell reconstitution in humanized mice

“…This appeared not to be the case as our results show that the human TCR Vβ repertoire in the SI IEL and SI LPL fractions of both N/S BLT and NSG-BLT mice were polyclonal, as has been described in young humans (Figure 5). 42 For a third comparison between normal human intestinal T cells and those in humanized mice, we took advantage of the fact that human intestinal T cells have an unambiguous surface phenotype that distinguishes them from human T cells in other tissues in the body. Specifically, on the surface of the CD8 + CD4 − T cells in the human SI, the CD8 receptor is typically a heterodimer composed of a CD8α molecule plus a CD8β molecule; however, on the surface of human intestinal CD8 + CD4 + T cells, the CD8 receptor is typically composed of a homodimer of two CD8α chains (CD8αα).…”

How colonization by microbiota in early life shapes the immune system

“…Normalization of these morphological and cellular defects in αβ T cells can be achieved by reintroducing standard mouse or human microbiota in adult mice (33–36). Furthermore, characterization of the TCR repertoire in intestinal tissues at the time of initial commensalization suggests an influx of polyclonal TCR-αβ + T cells early in life that lose diversity and revert to an oligoclonal state in the adult (37). To address this, subsequent studies comparing colonized and monocolonized mice with GF animals have begun to clarify the role of distinct commensal bacterial communities in modulating specific T cell effects.…”