Epitope Motifs Research Articles

Sequence homologies between hsp60 and autoantigens

The human heat shock protein (hsp) 60 shares sequence homology with a wide range of autoantigens including those of insulin dependent diabetes mellitus, Hashimoto's thyroiditis, glomerulonephritis, scleroderma, pemphigoid, rheumatoid arthritis, multiple sclerosis, chronic active hepatitis, primary biliary cirrhosis and Addison's disease. Here we shots the extent of this homology and suggest that it contributes to autoimmunity through cross-reactivity between hsp60 and tissue-specific proteins containing similar epitope motifs. Differences between individuals in MHC class II may influence the selection of a particular hsp60 epitope and the corresponding target antigen that gives rise to an autoimmune disease.

The immune response to measles virus in mice: T-helper response to the nucleoprotein and mapping of the T-helper epitopes

The T-helper response to the measles virus nucleoprotein (NP) has been studied in mice. The T-cell proliferative response was measured in lymphocytes from mice immunized with either a vaccinia measles-NP recombinant virus or a mouse neuro-adapted measles virus. A T-cell response was obtained with lymphocytes from H2d or H2k mice when stimulated with either measles virus or the NP expressed in bacteria. The response was CD4 + specific. The T-helper epitopes were mapped using truncated NP peptides. The major epitopes in both H2d and H2k mice were determined to be between amino acids 67–98. A further T-cell epitope (between amino acids 457–525) was identified when H2d mice were immunized with measles virus. Studies to quantitate the precursor cells for these epitopes confirmed that the region 67–98 of NP was immunodominant in both haplotypes immunized with the vaccinia-NP recombinant virus, whereas an additional major epitope was observed in the measles virus-infected H2d mice. The primary structure of the epitopes determined here are compared to predicted T-cell epitope motifs.

T cell recognition of Neisseria meningitidis class 1 outer membrane proteins. Identification of T cell epitopes with selected synthetic peptides and determination of HLA restriction elements.

No vaccine is yet available against serogroup B meningococci, which are a common cause of bacterial meningitis. Some outer membrane proteins (OMP), LPS, and capsular polysaccharides have been identified as protective Ag. The amino acid sequence of the protective B cell epitopes present within the class 1 OMP has been described recently. Synthetic peptides containing OMP B cell epitopes as well as capsular polysaccharides or LPS protective B cell epitopes have to be presented to the immune system in association with T cell epitopes to achieve an optimal Ir. The use of homologous, i.e., meningococcal, T cell epitopes has many advantages. We therefore investigated recognition sites for human T cells within the meningococcal class 1 OMP. We have synthesized 16 class 1 OMP-derived peptides encompassing predicted T cell epitopes. Peptides corresponding to both surface loops and trans-membrane regions (some of which occur as amphipathic beta-sheets) of the class 1 OMP were found to be recognized by T cells. In addition, 10 of 11 peptides containing predicted amphipathic alpha-helices and four of five peptides containing T cell epitope motifs according to Rothbard and Taylor (Rothbard, J. B., and W. R. Taylor. 1988. EMBO J 7:93) were recognized by lymphocytes from one or more volunteers. Some of the T and B cell epitopes were shown to map to identical regions of the protein. At least six of the peptides that were found to contain T cell epitopes show homology to constant regions of the meningococcal class 3 OMP and the gonococcal porins PIA and PIB. Peptide-specific T cell lines and T cell clones were established to investigate peptide recognition in more detail. The use of a panel of HLA-typed APC revealed clear HLA-DR restriction patterns. It seems possible now to develop a (semi-) synthetic meningococcal vaccine with a limited number of constant T cell epitopes that cover all HLA-DR locus products.

Antigenic variation of poliovirus studied by means of monoclonal antibodies.

The natural distribution of poliovirus neutralization epitopes was studied on several field isolates of each of the three serotypes by a neutralization index test for which a panel of homotypic monoclonal antibodies was used. Two categories of neutralization epitopes were detected: strain-specific or variable epitopes, and cross-reacting or common epitopes. The latter tended to be conserved among homotypic viruses. Some of the Sabin-specific neutralization epitopes were found to be mutually exclusive of wild-type epitopes, but coexistence of Sabin-specific and wild-type epitopes was found in other cases. During virus excretion by infants fed type 1 Sabin vaccine, the Sabin-specific neutralization epitope was lost, and sometimes the original epitope motif of the parental wild (Mahoney) virus was recovered. Epitope variation was also expressed by loss of epitope function in virus neutralization without modification of antigenic conformation.