Immune responses against human papillomavirus (HPV) type 16 virus-like particles in a cohort study of women with cervical intraepithelial neoplasia I. Differential T-helper and IgG responses in relation to HPV infection and disease outcome

T-helper (Th) cell-dependent IL-2 production and plasma IgG responses to vi rus-like particles consisting of the human papillomavirus type 16 (HPV-16) major capsid protein L1 (L1-VLP) were determined in patients with cytologic al evidence of cervical intraepithelial neoplasia (CIN) participating in a non-intervention prospective cohort study. lgG responses were associated wi th HPV-16 persistence and high-grade CIN lesions, while high frequencies of Th responses were observed in patients with both virus clearance and virus persistence, irrespective of CIN grade, The lgG response was found in conj unction with an IL-2 response to L1-VLP in 87% of the patients. Recognition of the HPV-16 L1 Th epitope (amino acids 311-335) was found to be more clo sely associated than recognition of L1-VLP as a whole to HPV exposure and C IN development. Among the HPV-16(+) patients included in this study, those showing a Th response to amino acids 311-335 were more likely to carry the HLA DRB1*11/DQB1*0301 haplotype, while those showing an IgG response to L1- VLP were more likely to carry DRB1*0101/DQB1*0501. However, neither cell-me diated nor humoral immune responses against HPV-16 L1 appear to be sufficie nt for the natural control of HPV infection and CIN development.