Previous studies suggested that tetanus and diphtheria toxoids (TTD and DTD
, respectively) contain "universal" epitopes for human CD4(+) cells (residu
es 632-651 and 950-969 of TTD and 271-290, 321-350, 351-370, 411-430, and 4
31-450 of DTD). To investigate whether CD4(+) cells of 100 randomly selecte
d subjects recognized those sequences, the proliferation of CD4+ cell-enric
hed blood lymphocytes to TTD and DTD and individual synthetic universal epi
topes was measured. CD4(+) cells of 98 subjects recognized both toroids, th
ose of 1 subject only TTD, and those of 1 only DTD. The TTD peptides and DT
D peptides 271-290 and 331-350 were recognized by greater than or equal to
80% of the toroid-sensitized subjects. The other DTD sequences were recogni
zed by 63%-71% of subjects, DR-homozygous subjects recognized several unive
rsal epitopes less frequently than did DR-heterozygous subjects. The intens
ity of responses to the epitope peptides correlated with that to TTD or DTD
, consistent with recognition of the peptides by CD4(+) cells specific for
the cognate toroid.