??T cell receptors expressed by CD4(-)CD8??(-) intraepithelial T cells drive their fate into a unique lineage with unusual MHC reactivities.

ABSTRACT: Coreceptor CD4 and CD8?? double-negative (DN) TCR??(+) intraepithelial T cells, although numerous, have been greatly overlooked and their contribution to the immune response is not known. Here we used T cell receptor (TCR) sequencing of single cells combined with retrogenic expression of TCRs to study the fate and the major histocompatibility complex (MHC) restriction of DN TCR??(+) intraepithelial T cells. The data show that commitment of thymic precursors to the DN TCR??(+) lineage is imprinted by their TCR specificity. Moreover, the TCRs they express display a diverse and unusual pattern of MHC restriction that is nonoverlapping with that of CD4(+) or CD8??(+) T cells, indicating that they sense antigens that are not recognized by the conventional T cell subsets. The new insights indicate that DN TCR??(+) T cells form a third lineage of TCR?? T lymphocytes expressing a variable TCR repertoire, which serve nonredundant immune functions.

SUBMITTER: Mayans S 

PROVIDER: S-EPMC4142827 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature