A large degree of functional diversity exists among helper T cells specific for the same antigenic site of influenza hemagglutinin.
The site-1 determinant of the hemagglutinin molecule of influenza virus (A/PR/8/34) is one of several immunodominant sites in the BALB/c Th cell response to Ha. A synthetic peptide comprising this T cell site (HA110-120), a panel of analogs containing single substitutions in this determinant, and homologs truncated at the amino- or carboxyl-terminal were used to examine the fine specificities of 15 T cells specific for site-1 in the context of I-Ed. The results indicate that every residue within the minimal determinant plays a role in the T cell recognition process, as single substitutions at any of these positions affected the ability of the peptide to stimulate at least some site 1-specific T cells. For the majority of the residues examined, substitutions had dissimilar effects on distinct T cells, indicating that the substituted residues were affecting recognition in a receptor-specific manner. Each of the 15 T cells examined had a distinct fine specificity pattern, suggesting that the BALB/c T cell repertoire for this site is likely to exceed 100 distinct clonotypes.
Wistar Institute of Anatomy and Biology, Philadelphia, PA 19104.
A M
AM
Haberman
C
C
Moller
D
D
McCreedy
W U
WU
Gerhard
D000595:Amino Acid Sequence; D000818:Animals; D000939:Epitopes; D006389:Hemagglutinins, Viral / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006825:Hybridomas / Q000276:immunology; D009980:Influenza A virus / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000138:chemical synthesis / Q000276:immunology; D013329:Structure-Activity Relationship; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D000939:Epitopes; D006389:Hemagglutinins, Viral; D000949:Histocompatibility Antigens Class II; C024138:I-E-antigen; D009842:Oligopeptides