Former studies have shown that the class 5 outer membrane proteins (Opa and Ope proteins) of Neisseria meningitidis are at least as immunogenic as meningococcal porin proteins, High antibody titers to class 5 proteins have been observed in sera obtained during convalescence after meningococcal infection. A strong increase in anti-class 5 antibodies has also been observed in vaccinees who received a meningococcal outer membrane vesicle preparation. Tire enhanced B-cell response to class 5 proteins may be due to the presence of immunodominant helper T-cell epitopes in these proteins. In order to investigate this hypothesis, we tested purified Opa, OpC, and class 1 proteins for recognition try human T cells. A hierarchy of T-cell immunogenicity was observed among the enter membrane proteins, the Opa protein being more immunogenic then the other proteins. In most cases, the proliferative responses elicited by Ope were higher than the responses observed for the class I protein. The epitopes recognized by the immune T cells were identified by using overlapping synthetic peptides spanning the protein sequences of OpaB, Opa5d, and Opc.