T-cell responses to outer membrane proteins of Neisseria meningitidis: comparative study of the Opa, Opc, and PorA proteins

Abstract

Former studies have shown that the class 5 outer membrane proteins (Opa and Opc 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. The 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 by human T cells. A hierarchy of T-cell immunogenicity was observed among the outer membrane proteins, the Opa protein being more immunogenic than the other proteins. In most cases, the proliferative responses elicited by Opc were higher than the responses observed for the class 1 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.

Analysis of Neisseria lactamica antigens putatively implicated in acquisition of natural immunity to Neisseria meningitidis

“…Opa proteins (26^30 kDa) are immunogenic but highly variable [24]. Our results show that Opa proteins are present in ¢ve of six N. meningitidis strains tested, but their expression di¡ers between strains (two or three Opa proteins are expressed depending on strain).…”

Two‐dimensional structure of the Opc invasin from Neisseria meningitidis

“…Of the 40 18-mer peptides overlapping by 12 amino acids tested as T-cell helper epitopes by Wiertz et al (1996), those which most uniformly stimulated human Tcell proliferation were located in predicted transmembrane strands 1, 3, 4, 6 and 7 (peptides 2, 9, 16, 23 and 26)…”

“…The identification of five permissive sites which do not prevent folding and which are exposed on the cell surface raises the possibility of using the Opc protein in vaccine development as a carrier protein for epitopes from foreign antigens. The Opc protein is known to be highly immunogenic in humans (de Cossio et al, 1992;Rosenqvist et al, 1993) and contains several strong T-cell epitopes in transmembrane strands which stimulate proliferation of human T cells (Wiertz et al, 1996), unlike many other OMPs for which immunogenicity has only been tested in animal models. Experiments would be needed to determine which of the permissive sites would be most efficient at presenting foreign epitopes to the immune system.…”

“…Opc-mediated adhesion and invasion is inhibited by two of these antibodies (Virji et al, 1992) and three are known to be bactericidal (Rosenqvist et al, 1993;1995), suggesting that their epitopes are exposed on the cell surface. The Opc protein contains Tcell epitopes which stimulate proliferation of human T cells (Wiertz et al, 1996), which have also not yet been mapped. We therefore decided to make a structural model of the Opc protein, map B-and T-cell epitopes, and test the model experimentally.…”

Production of a T‐Cell Clone Which Reacts with Membrane Proteins of Acholeplasma laidlawii

“…A 17-kDa lipoprotein derived from the membrane of Francisella tularensis was reported to activate T cells which could produce IL-2 and interferon (IFN)-y (16). Recently, Wiertz et al (18) reported that human T cells responded to the outer-membrane proteins of Neisseria meningitidis. These findings indicate that the cellular immune response to bacterial membrane proteins may play a role in protection against infection.…”