[alpha][beta]T Cell Receptors Expressed by CD4-CD8[alpha][beta]-Intraepithelial T Cells Drive Their Fate into a Unique Lineage with Unusual MHC Reactivities

• Published in: Immunity (Cambridge, Mass.) Mass.), 2014-08, Vol.41 (2), p.207
• Main Authors: Mayans, Sofia, Stepniak, Dariusz, Palida, Sakina F, Larange, Alexandre, Dreux, Joanna, Arlian, Britni M, Shinnakasu, Ryo, Kronenberg, Mitchell, Cheroutre, Hilde, Lambolez, Florence
• Format: Article
• Language: English
• Subjects: Cloning; Immune system; Laboratory animals; Lymphocytes; Statistical analysis; T cell receptors
• ISSN: 1074-7613; 1097-4180
• DOI: 10.1016/j.immuni.2014.07.010

Coreceptor CD4 and CD8[alpha]β double-negative (DN) TCR[alpha]β+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[alpha]β+intraepithelial T cells. The data show that commitment of thymic precursors to the DN TCR[alpha]β+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[alpha]β+T cells, indicating that they sense antigens that are not recognized by the conventional T cell subsets. The new insights indicate that DN TCR[alpha]β+T cells form a third lineage of TCR[alpha]β T lymphocytes expressing a variable TCR repertoire, which serve nonredundant immune functions.