Old and New World arenaviruses share a highly conserved epitope in the fusion domain of the glycoprotein 2, which is recognized by Lassa virus-specific human CD4+ T-cell clones.
Data from human studies and animal experiments indicate a dominant role of T-cells over antibodies in controlling acute Lassa virus infection and providing immunity to reinfection. Knowledge of the epitopes recognized by T-cells may therefore be crucial to the development of a recombinant Lassa virus vaccine. In order to study human T-cell reactivity to the most conserved structural protein of Lassa virus, the glycoprotein 2 (GP2), seven GP2-specific CD4+ T-cell clones (TCCs) were generated from the lymphocytes of a Lassa antibody positive individual. All TCC displayed high specific proliferation, showed DR-restriction, and produced IFN-gamma upon stimulation with recombinant GP2. The epitope of four of the clones was localized to a short stretch of 13 amino acids located in the N-terminal part of GP2 (aa 289-301, numbering according to sequence of GPC). This epitope is conserved in all strains of Lassa virus and lymphocytic choriomeningitis virus (LCMV), shows >90% similarity in all New World arenaviruses of clade B, and overlaps with the proposed fusion domain of GP2. Peptides with conservative aa exchanges, as they naturally occur in the epitope 289-301 of the Old World arenavirus Mopeia and some New World arenaviruses, continued to effectively stimulate the Lassa-GP2-specific T-cell clones tested. The finding of a human T-helper cell epitope, which is highly conserved between Old and New World arenaviruses, is of importance for the design of arenavirus vaccines.
Meulen
Jan ter
Jt
Institute of Virology, Philipps University, 35037 Marburg, Germany. j.termeulen@crucell.com
Badusche
Marlis
M
Satoguina
Judith
J
Strecker
Thomas
T
Lenz
Oliver
O
Loeliger
Cornelius
C
Sakho
Mohamed
M
Koulemou
Kekoura
K
Koivogui
Lamine
L
Hoerauf
Achim
A
D000595:Amino Acid Sequence; D018050:Arenavirus / Q000235:genetics / Q000276:immunology*; D001782:Blood Donors; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002455:Cell Division; D002999:Clone Cells; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology*; D005260:Female; D006023:Glycoproteins / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007836:Lassa virus / Q000235:genetics / Q000276:immunology; D008297:Male; D008969:Molecular Sequence Data; D010455:Peptides / Q000235:genetics / Q000494:pharmacology; D016415:Sequence Alignment; D013045:Species Specificity; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology*
D018984:Epitopes, T-Lymphocyte; D006023:Glycoproteins; D010455:Peptides; D014759:Viral Envelope Proteins; C077198:glycoprotein gp2, lassa virus