GSBS Student Publications

Title

Human cytotoxic T-lymphocyte repertoire to influenza A viruses

GSBS Program

Biochemistry & Molecular Pharmacology

UMMS Affiliation

Graduate School of Biomedical Sciences; Program in Immunology and Virology; Center for Infectious Disease and Vaccine Research

Date

10-10-1998

Document Type

Article

Medical Subject Headings

Adult; Animals; Antigens, Viral; Cell Line; Cross Reactions; Epitope Mapping; Epitopes; HLA Antigens; Humans; Immunologic Memory; Influenza A virus; Interferon Type II; Mice; Neuraminidase; T-Lymphocytes, Cytotoxic; Viral Matrix Proteins; Viral Proteins

Disciplines

Life Sciences | Medicine and Health Sciences

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.

Rights and Permissions

Citation: J Virol. 1998 Nov;72(11):8682-9.

Related Resources

Link to article in PubMed

Journal Title

Journal of virology

PubMed ID

9765409