MOUSE CD1-AUTOREACTIVE T-CELLS HAVE DIVERSE PATTERNS OF REACTIVITY TOCD1(+) TARGETS

Humans and mice contain significant populations of T cells that are re active for autologous CD1 molecules, Using a panel of five mouse CD1 ( mCD1)-autoreactive T cell hybridomas, we show here that this autoreact ivity does not correlate,vith the level of CD1 expression, In some cas es, these autoreactive T cells can distinguish between different cell types that express the same CD1 molecule, suggesting that some factor in addition to CD1 expression is critical for autoreactive T cell stim ulation, To determine whether a CD1-bound ligand may be required, we e xpressed mutant mCD1 molecules that are defective for the putative end osomal localization sequence in the cytoplasmic domain, We demonstrate that mCD1, like its human CD1 homologues, is found in endosomes, and that it colocalizes extensively with the DM molecule, We further demon strate, by site-directed mutagenesis, that the tyrosine in the cytopla smic sequence is required for this endosomal Localization, A T cell hy brid expressing V beta 8 and V alpha 14, the major TCR expressed by NK 1(+) T cells, exhibited greatly diminished reactivity to mutant CD1 mo lecules that do not traffic through endosomes, although the reactivity of other T cell hybrids to this mutant was not greatly affected, Ther efore, we propose that at least some of the autoreactive T cells requi re endosomally derived CHI-hound ligands, and that they are capable of distinguishing between a diverse set of such self-ligands, which migh t be either autologous lipoglycans or peptides.