Identification of Mengo virus T helper cell epitopes.
To identify Mengo virus-specific T cell epitopes in mice (the natural host for the virus), lymph node cells were obtained from BALB/c (H-2d) mice, previously immunized with u.v.-inactivated virus, and stimulated in vitro with each of 116 overlapping peptides (10 to 18 residues long) covering the entire capsid coding region (834 amino acids). T cell epitopes were defined on the basis of specific peptide-induced lymphocyte proliferation. Where proliferation occurred, immunological characterization showed that it was the CD4+ T helper (Th) cell subpopulation that was responsible for the Mengo virus-specific response. Surprisingly, no Mengo virus Th cell epitopes were found in capsid protein VP1 or VP4. Six peptides in VP2 (residues 1 to 15, 99 to 108, 118 to 132, 133 to 147, 227 to 236 and 247 to 256) identified the positions of separate Th cell epitopes, and two overlapping peptides (residues 173 to 182 and 178 to 192) defined an additional Th cell immunogenic sequence. Three individual peptides in VP3 (residues 46 to 58, 136 to 150 and 198 to 212) and two overlapping peptides (residues 1 to 15 and 11 to 20) also represent Th cell epitopes. Similar assays with C57BL/6 (H-2b) and SJL/J (H-2s) mice showed that the pattern of recognition of these peptides was H-2 restricted. Each of the previously identified sites of B cell antigenicity in VP2 and VP3 are associated with one Th epitope. Comparison of the experimentally determined Th epitopes with potential T cell epitopes identified by several predictive strategies revealed only a low correlation between authentic and predicted epitopes.
Muir
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Department of Molecular Biology, Research Institute Scripps Clinic, La Jolla, California 92037.
Kobasa
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Bittle
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Scraba
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D000595:Amino Acid Sequence; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D002213:Capsid / Q000096:biosynthesis / Q000737:chemistry / Q000276:immunology*; D036022:Capsid Proteins; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000032:analysis; D005260:Female; D007739:L Cells; D008198:Lymph Nodes / Q000276:immunology / Q000821:virology; D008213:Lymphocyte Activation; D008574:Mengovirus / Q000276:immunology* / Q000302:isolation & purification; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D017433:Protein Structure, Secondary; D013601:T-Lymphocytes / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000821:virology
D000914:Antibodies, Viral; D036022:Capsid Proteins; D000939:Epitopes