Nm. Chiu et al., The selection of M3-restricted T cells is dependent on M3 expression and presentation of N-formylated peptides in the thymus, J EXP MED, 190(12), 1999, pp. 1869-1878
The major histocompatibility complex (MHC) class Ib molecule H2-M3 binds N-
formylated peptides from mitochondria and bacteria. To explore the role of
MS expression and peptide supply in positive and negative selection, we gen
erated transgenic mice expressing an M3-restricted TCR-alpha/beta from a CD
8(+) T cell hybridoma (D7) specific for a listerial peptide (LemA). Develop
ment of M3-restricted transgenic T cells is impaired in both beta 2-microgl
obulin-deficient and transporter associated with antigen processing (TAP)-d
eficient mice, but is not diminished by changes in the H-2 haplotype. Matur
ation of M3/LemA-specific CD8(+) single positive cells in fetal thymic orga
n culture was sensitive to M3 expression levels as determined by antibody b
locking and use of the castaneus mutant allele of M3. positive selection wa
s rescued in TAP(-/-) lobes by nonagonist mitochondrial and bacterial pepti
des, whereas LemA and a partial agonist variant caused negative selection.
Thus, MS-restricted CD8(+) T cells are positively and negatively selected b
y M3, with no contribution from the more abundant class Ia molecules. These
results demonstrate that class Ib molecules can function in thymic educati
on like class Ia molecules, despite limited ligand diversity and low levels
of expression.