L. Brossay et al., MOUSE CD1-AUTOREACTIVE T-CELLS HAVE DIVERSE PATTERNS OF REACTIVITY TOCD1(+) TARGETS, The Journal of immunology, 160(8), 1998, pp. 3681-3688
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.