Ligand requirements for natural (NK1+) T cell development

Natural T (NT) cells are an unusual population of thymocytes with phenotypic features of activated/memory αβ+ T cells as well as natural killer (NKRP-1, IL-2Rβ, FcεRIγ) cells. Their function(s) is predicted to be immunoregulatory in nature. Positive selection of NT cells requires a conserved β2-microglobulin associated molecule(s) displayed by CD4+8+ thymocytes, implicating CD1 and Tla as the selecting ligand. The control of positive selection by CD1 would be predicted from the recent in vitro studies, however, whether Tla plays a role in this process is not known. By a quantitative approach, using mice that lack Tla or co-express it with CD1, Tla's role in NT cell development was studied. If Tla's influence is positive or negative then one would predict that the absolute numbers of NT cells would increase or decrease, respectively, in Tla+ mice compared to Tla null mice. The data revealed that Tla+ mice have numerically expanded (2-5 fold) NT cell repertoire compared to Tla null mice. Further, this expansion did not compromise the proportion of each of the limited T cell receptor β chains expressed by the NT cells suggesting that the repertoire selected by Tla and CD1 are similar. Akin to CD1, the function of Tla in positive selection of NT cells is TAP1 independent. The fact that Tla displays N-terminally blocked self peptides suggests the recognition of TAP independent peptide(s) by NT cells. Thus we conclude that the function(s) of NT cells is Tla and CD1 restricted.