title: Tracking of peptide-specific CD4+ T-cell responses after an acute resolving viral infection: a study of parvovirus B19.
abstract: The evolution of peptide-specific CD4(+) T-cell responses to acute viral infections of humans is poorly understood. We analyzed the response to parvovirus B19 (B19), a ubiquitous and clinically significant pathogen with a compact and conserved genome. The magnitude and breadth of the CD4(+) T-cell response to the two B19 capsid proteins were investigated using a set of overlapping peptides and gamma interferon-specific enzyme-linked immunospot assays of peripheral blood mononuclear cells (PBMCs) from a cohort of acutely infected individuals who presented with acute arthropathy. These were compared to those for a cohort of B19-specific immunoglobulin M-negative (IgM(-)), IgG(+) remotely infected individuals. Both cohorts of individuals were found to make broad CD4(+) responses. However, while the responses following acute infection were detectable ex vivo, responses in remotely infected individuals were only detected after culture. One epitope (LASEESAFYVLEHSSFQLLG) was consistently targeted by both acutely (10/12) and remotely (6/7) infected individuals. This epitope was DRB1*1501 restricted, and a major histocompatibility complex peptide tetramer stained PBMCs from acutely infected individuals in the range of 0.003 to 0.042% of CD4(+) T cells. Tetramer-positive populations were initially CD62L(lo); unlike the case for B19-specific CD8(+) T-cell responses, however, CD62L was reexpressed at later times, as responses remained stable or declined slowly. This first identification of B19 CD4(+) T-cell epitopes, including a key immunodominant peptide, provides the tools to investigate the breadth, frequency, and functions of cellular responses to this virus in a range of specific clinical settings and gives an important reference point for analysis of peptide-specific CD4(+) T cells during acute and persistent virus infections of humans.
authors.affiliation: Partners AIDS Research Center, Massachusetts General Hospital, Harvard Medical School, 149 13th Street, Charlestown, MA 02129, USA. vkasprowicz@partners.org
authors.forename: Victoria
authors.initials: V
authors.lastname: Kasprowicz
authors.forename: Adiba
authors.initials: A
authors.lastname: Isa
authors.forename: Thomas
authors.initials: T
authors.lastname: Tolfvenstam
authors.forename: Katie
authors.initials: K
authors.lastname: Jeffery
authors.forename: Paul
authors.initials: P
authors.lastname: Bowness
authors.forename: Paul
authors.initials: P
authors.lastname: Klenerman
mesh_terms: D000328:Adult; D000914:Antibodies, Viral / Q000097:blood; D001168:Arthritis / Q000276:immunology / Q000821:virology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D036022:Capsid Proteins / Q000276:immunology; D002478:Cells, Cultured; D015331:Cohort Studies; D000939:Epitopes / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D007371:Interferon-gamma / Q000096:biosynthesis; D019041:L-Selectin / Q000032:analysis; D007963:Leukocytes, Mononuclear / Q000276:immunology; D016131:Lymphocyte Subsets / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010322:Parvoviridae Infections / Q000276:immunology*; D016732:Parvovirus B19, Human / Q000276:immunology*; D010455:Peptides / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D036022:Capsid Proteins; D000939:Epitopes; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D010455:Peptides; D019041:L-Selectin; D007371:Interferon-gamma