Recognition of homo- and heterosubtypic variants of influenza A viruses by human CD8+ T lymphocytes.
In the present study, the recognition of epitope variants of influenza A viruses by human CTL was investigated. To this end, human CD8(+) CTL clones, specific for natural variants of the HLA-B*3501-restricted epitope in the nucleoprotein (NP(418-426)), were generated. As determined in (51)Cr release assays and by flow cytometry with HLA-B*3501-peptide tetrameric complexes, CTL clones were found to be specific for epitopes within one subtype or cross-reactive with heterosubtypic variants of the epitope. Using eight natural variants of the epitope, positions in the 9-mer important for T cell recognition and involved in escape from CTL immunity were identified and visualized using multidimensional scaling. It was shown that positions 4 and 5 in the 9-mer epitope were important determinants of T cell specificity. The in vivo existence of CD8(+) cells cross-reactive with homo- and heterosubtypic variants of the epitope was further confirmed using polyclonal T cell populations obtained after stimulation of PBMC with different influenza A viruses. Based on the observed recognition patterns of the clonal and polyclonal T cell populations and serology, it is hypothesized that consecutive infections with influenza viruses containing different variants of the epitope select for cross-reactive T cells in vivo.
Boon
Adrianus C M
AC
Department of Virology and WHO National Influenza Center, Erasmus MC, Rotterdam, The Netherlands.
de Mutsert
Gerrie
G
van Baarle
Debbie
D
Smith
Derek J
DJ
Lapedes
Alan S
AS
Fouchier
Ron A M
RA
Sintnicolaas
Kees
K
Osterhaus
Albert D M E
AD
Rimmelzwaan
Guus F
GF
D000328:Adult; D000956:Antigens, Viral / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D002461:Cell Line, Transformed; D002999:Clone Cells; D003601:Cytotoxicity Tests, Immunologic / Q000379:methods; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D015797:HLA-B35 Antigen / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D006801:Humans; D009980:Influenza A virus / Q000145:classification / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000737:chemistry / Q000276:immunology / Q000821:virology; D008875:Middle Aged; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding / Q000276:immunology; D012703:Serotyping; D013194:Staining and Labeling; D014758:Viral Core Proteins / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism
D000956:Antigens, Viral; D018984:Epitopes, T-Lymphocyte; D015797:HLA-B35 Antigen; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins; D010446:Peptide Fragments; D014758:Viral Core Proteins