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PMID: 9765409 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Human cytotoxic T-lymphocyte repertoire to influenza A viruses.

Journal of virology ·Vol. 72 ·No. 11 ·1998-11-00 ·Pages 8682-9

Jameson J, Cruz J, Ennis FA

Abstract

The murine CD8(+) cytotoxic-T-lymphocyte (CTL) repertoire appears to be quite limited in response to influenza A viruses. The CTL responses to influenza A virus in humans were examined to determine if the CTL repertoire is also very limited. Bulk cultures revealed that a number of virus proteins were recognized in CTL assays. CTL lines were isolated from three donors for detailed study and found to be specific for epitopes on numerous influenza A viral proteins. Eight distinct CD8(+) CTL lines were isolated from donor 1. The proteins recognized by these cell lines included the nucleoprotein (NP), matrix protein (M1), nonstructural protein 1 (NS1), polymerases (PB1 and PB2), and hemagglutinin (HA). Two CD4(+) cell lines, one specific for neuraminidase (NA) and the other specific for M1, were also characterized. These CTL results were confirmed by precursor frequency analysis of peptide-specific gamma interferon-producing cells detected by ELISPOT. The epitopes recognized by 6 of these 10 cell lines have not been previously described; 8 of the 10 cell lines were cross-reactive to subtype H1N1, H2N2, and H3N2 viruses, 1 cell line was cross-reactive to subtypes H1N1 and H2N2, and 1 cell line was subtype H1N1 specific. A broad CTL repertoire was detected in the two other donors, and cell lines specific for the NP, NA, HA, M1, NS1, and M2 viral proteins were isolated. These findings indicate that the human memory CTL response to influenza A virus is broadly directed to epitopes on a wide variety of proteins, unlike the limited response observed following infection of mice.

MeSH Terms
Adult Animals Antigens, Viral Cell Line Cross Reactions Epitope Mapping Epitopes HLA Antigens Humans Immunologic Memory In Vitro Techniques Influenza A virus/classification,immunology Interferon-gamma/biosynthesis Mice Neuraminidase/immunology T-Lymphocytes, Cytotoxic/immunology Viral Matrix Proteins/immunology Viral Proteins/immunology
Chemicals
Antigens, Viral Epitopes HLA Antigens Viral Matrix Proteins Viral Proteins Interferon-gamma Neuraminidase
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Jameson J
Center for Infectious Disease and Vaccine Research, University of Massachusetts Medical Center, Worcester, Massachusetts 01655, USA.
Cruz J
Ennis F A
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
Published
1998-11-00
Pages
8682-9
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC110281
Subset
IM
Grants
NIAID NIH HHS · T32 AI007349 · United States
NIAID NIH HHS · AI 07349 · United States
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