Identification of eight determinants in the hemagglutinin molecule of influenza virus A/PR/8/34 (H1N1) which are recognized by class II-restricted T cells from BALB/c mice

Abstract

Eight nonoverlappimg regions of the hemagglutinin (HA) molecule of influenza virus A/PR/8/34 (PR8), which serve as recognition sites for class II-restricted T cells (TH) from BALB/c mice, have been identified in the form of 10to 15-amino-acid-long synthetic peptides. These TH determinants are located between residues 110 to 313 of the HA1 polypeptide. From a total of 36 HA-specific TH clones and limiting-dilution cultures of independent clonal origins, 33 (90%) responded to stimulation with one of these peptides. The residual three TH clones appeared to recognize a single additional determinant on the HA1 polypeptide which could not be isolated, however, in the form of a stimulatory peptide. None of the motifs that have been proposed to typify TH determinants were displayed by more than half of these recognition sites. Most unexpected was the finding that none of the TH determinants was located in the ectodomain of the HA2 polypeptide that makes up roughly one-third of the HA molecule. Possible reasons for the preferential recognition of HA1 as opposed to HA2 by TH are discussed.

Cellular Immune Responses to Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) Infection in Senescent BALB/c Mice: CD4+T Cells Are Important in Control of SARS-CoV Infection

“…Transfer of virusspecific CD8 ϩ T cells can provide protection and independently mediate viral clearance (45). CD4 ϩ T cells are less efficient than CD8 ϩ T cells at clearing influenza virus (19), and CD4 ϩ T-cell-mediated protection occurs through Ab-dependent mechanisms (46) and Ab-independent direct killing mechanisms that require perforin (4). In the senescent mouse model for SARS, depletion of CD4 ϩ T cells results in reduced production of neutralizing Ab and Th1 and Th2 cytokines and pulmonary recruitment of inflammatory cells.…”

A Triclade DNA Vaccine Designed on the Basis of a Comprehensive Serologic Study Elicits Neutralizing Antibody Responses against All Clades and Subclades of Highly Pathogenic Avian Influenza H5N1 Viruses

“…Briefly, spleens were harvested from triclade DNA-and empty vector-vaccinated mice and gently homogenized into a single-cell suspension. After erythrocyte lysis, the splenocytes (10 6 cells/ well) were stimulated with two HA peptides (IYSTVASSL and LYEKV RLQL [11,19,25], 2.5 g/ml for each peptide) and anti-CD28 and anti-CD49d antibodies (BD Pharmingen, 1 g/ml) in 24-well tissue culture plates (Costar; Corning) at 37°C. Two hours later, brefeldin A (BD Biosciences, 10 g/ml) was added.…”

Activation of CD4+CD25+ regulatory T cell suppressor function by analogs of the selecting peptide

“…Mice TS1 and TS1ÂHA28 mice have been previously described [8]. TS2 mice correspond to the HNT-TCR previously described [33], and encode a transgenic TCR specific for the major I-Ad restricted determinant of PR8 HA (S2) [34]. Mice were maintained in sterile microisolators at the Wistar Institute Animal Facility.…”