INDUCTION OF CYTOTOXIC T-CELL RESPONSE BY OPTIMAL-LENGTH PEPTIDES DOES NOT REQUIRE CD4(-CELL HELP() T)

In several experimental models, synthetic peptides were shown to activ ate efficiently cytotoxic T-lymphocyte (CTL) responses and therefore r epresent an attractive strategy to develop new vaccines. However, the mechanisms by which they induce CTL responses are not yet fully unders tood. Several studies using 15-16-mer peptides previously demonstrated that CD4(+) helper T cells are required to induce optimal CTL respons es with synthetic peptides. However, recently, it was suggested that s horter 8-12-mer peptides could have an increased in vivo immunogenicit y. In the present study, we therefore investigated if such optimal-len gth peptides still require CD4(+) T-cell help to activate CTL response s. To address this question, three synthetic peptides containing diffe rent viral CTL epitopes were injected into mice depleted of CD4(+) or CD8(+) T cells using specific monoclonal antibodies or into mice genet ically deficient in those T-cell populations. Our results clearly esta blished that activation of CTL responses by those short optimal peptid es does not require CD4(+) T-cell help and therefore suggested that hi gh-density binding of peptides to major histocompatibility complex cla ss I molecules on the surface of antigen-presenting cells is required for direct activation of CD8(+) T cells, independently of CD4(+) T-cel l help.