We previously reported that the frequency of TCRBV2 and TCRBV6S5-bearing T-cells was high in patients in the acute phase of Kawasaki disease (KD) and that streptococcal pyrogenic exotoxin C (SPE-C) was a potent stimulator of these TCRBV-bearing T-cells. To further elucidate the pathogenesis of KD, we examined the T-cell receptor (TCR) repertoire, human leukocyte antigen (HLA)-DRB1 genotype, and antibody responses to recombinant(r) SPE-C in patients with KD. We also performed in vitro stimulation with rSPE-A and rSPE-C of peripheral blood mononuclear cells from healthy donors and characterized the reacting T-cells. The percentage of T-cells bearing TCRBV2 and TCRBV6S5 was high in patients in the acute stage of KD. rSPE-C stimulation of PBMC from healthy donors induced expansion of TCRBV2 and TCRBV6S5-bearing T-cells. Furthermore, serum levels of anti-SPEC antibodies, which did not display antimitogenic activity, were higher in patients with acute KD than in age-matched controls. The frequencies of the DRB1*04051, 0406, and 0901 were high, whereas that of the DRB1*1101 was low among patients with KD as compared with the healthy adults.