Genome-wide screening of human T-cell epitopes in influenza A virus reveals a broad spectrum of CD4(+) T-cell responses to internal proteins, hemagglutinins, and neuraminidases.
We performed a genome-wide screening for T-cell epitopes using synthetic peptides that encompass all of the influenza A viral proteins, including subtype variants for hemagglutinin (HA; H1, H3, and H5) and neuraminidase (NA; human and avian N1 and N2) proteins, based on the sequence information of recently circulating strains. We identified a total of 83 peptides, 54 of them novel, to which specific T cells were detectable in interferon-gamma (IFN-gamma) enzyme-linked immunosorbent spot assays using peripheral blood mononuclear cells from four healthy adult donors. The surface glycoproteins, HA and NA, major components of vaccines, expressed many T-cell epitopes. HA and matrix protein 1 expressed more T-cell epitopes than other viral proteins, most of which were recognized by CD4(+) T cells. We established several cytotoxic CD4(+) T-cell lines from these donors. We also analyzed H1 and H3 HA-specific T-cell responses using the peripheral blood mononuclear cells of 30 hospital workers. Fifty-three percent of donors gave a positive response to H3 HA peptides, whereas 17% gave a positive response to H1 HA peptides. Our genome-wide screening is useful in identifying T-cell epitopes and is complementary to the approach based on the predicted binding peptides to well-studied HLA-A, -B, and -DR alleles.
Babon
Jenny Aurielle B
JA
Center for Infectious Disease and Vaccine Research, University of Massachusetts Medical School, Worcester, MA 01655, USA.
Cruz
John
J
Orphin
Laura
L
Pazoles
Pamela
P
Co
Mary Dawn T
MD
Ennis
Francis A
FA
Terajima
Masanori
M
D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D002460:Cell Line; D003429:Cross Reactions; D003602:Cytotoxicity, Immunologic; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D016679:Genome, Viral / Q000276:immunology; D055106:Genome-Wide Association Study; D006388:Hemagglutinins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D006650:Histocompatibility Testing; D006801:Humans; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology*; D007371:Interferon-gamma / Q000378:metabolism; D009439:Neuraminidase / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D014763:Viral Matrix Proteins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D014764:Viral Proteins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*
D018984:Epitopes, T-Lymphocyte; D006388:Hemagglutinins; C488936:M1 protein, Influenza A virus; D010446:Peptide Fragments; D014763:Viral Matrix Proteins; D014764:Viral Proteins; D007371:Interferon-gamma; D009439:Neuraminidase