IMMUNOGENICITY OF A CONTIGUOUS T-B SYNTHETIC EPITOPE OF THE A PR/8/34INFLUENZA-VIRUS/

A contiguously linked T-B synthetic viral epitope ((110)HA(120)-(150)H A(159),T-B) was investigated for its potency in inducing humoral and c ellular immune responses in vivo, The T-cell epitope (110)HAL(120) cor responds to the site 1 hemagglutinin (HA) of the A/PR/8/34 (PR8) influ enza virus and is recognized by CD4 T cells in association with I-E-d class II major histocompatibility complex molecules, The (150)HA(159) represents a major B-cell epitope of the KA protein, T-B dipeptide emu lsified in Freund's complete adjuvant was able to induce strong antivi ral antibody titers and a high frequency of specific T-cell precursors after a single inoculation in BALB/c mice, In contrast, immunization under identical conditions,vith equimolar mixtures of T and B peptides did not elicit antibody titers or a cellular immune response. As indi cated by the isotypes of antiviral antibodies, the T-B dipeptide prefe rentially induced a Th1-like immune response, Challenge with T-B dipep tide, but not with T or B peptide alone, stimulated peptide-specific T memory cells in mice previously primed,vith PR8 virus or with T-B dip eptide, As a consequence, 71 and 57% of these mice, respectively, surv ived infection with two 100% lethal doses of PR8 virus, Our results su ggest that, inasmuch as contiguity between T- and B-cell epitopes prov ides enough signaling capacity to trigger the mechanisms of T-B-cell c ooperation in vivo, a T-B contiguous epitope may well represent a mini mal built-in subunit vaccine. Aside from their potential bioavailabili ty, the T-B contiguous epitopes may also represent attractive tools fo r investigating the molecular mechanisms of T-B-cell cooperation respo nsible for antiviral protection.