We present the first evidence of a T lymphocyte response to N-formylated pe
ptides in humans. N-formylated peptide sequences from self (mitochondrial)
and foreign (microbial) antigens were used to isolate antigen-specific T ce
ll clones from healthy individuals, including a set of monozygotic twins. T
he observed response differed from that previously described in mouse (CD4(
+) phenotype and MHC class II restriction in humans vs. CD8(+) phenotype an
d class I restriction in mice). These lymphocytes produce substantial amoun
ts of IFN-gamma. They were isolated in only one of the monozygotic twins, w
hich suggests that their expansion in the healthy immune repertoire is inde
pendent of the genetic background. Our result will help in assessing the re
levance of N-formylated peptide-specific T cells in protection against infe
ctions within the human immune system.