Recognition of the influenza hemagglutinin by class II MHC-restricted T lymphocytes and antibodies. I. Site definition and implications for antigen presentation and T lymphocyte recognition.
We have identified the site encompassing residues 126-145 on the A/Japan/57 influenza hemagglutinin molecule that is recognized in association with HLA-DRw11 by a clonal population of human, influenza specific, CD4+ cytolytic T lymphocytes. The critical core sequence of the T cell determinant spans hemagglutinin residues 129-140 and overlaps a putative antibody binding site. Hemagglutinins of influenza field strains that are not recognized by the T cell clones contain sequence alterations within the 129-140 target site of the CD4+ T cells. Functional analyses, with synthetic peptides, of the contribution of each of the residues within the sequence toward the capacity of the antigenic fragment to associate with both the restriction element and the TCR revealed a continuous linear array of residues necessary for MHC binding and/or Ag receptor engagement. At least one residue, the lysine at position 134, was shown to be critical for both DRw11 association and TCR recognition. The significance of these findings for recognition of glycoproteins by human CD4+ T cells is discussed.
Brown
L R
LR
Department of Pathology, Washington University School of Medicine, St. Louis, MO 63110.
Nygard
N R
NR
Graham
M B
MB
Bono
C
C
Braciale
V L
VL
Gorka
J
J
Schwartz
B D
BD
Braciale
T J
TJ
D000595:Amino Acid Sequence; D000938:Antigen-Presenting Cells / Q000276:immunology*; D001665:Binding Sites; D015704:CD4 Antigens / Q000276:immunology*; D000939:Epitopes / Q000032:analysis; D006684:HLA-DR Antigens / Q000276:immunology*; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006389:Hemagglutinins, Viral / Q000276:immunology*; D006801:Humans; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000378:metabolism*
D015704:CD4 Antigens; D000939:Epitopes; D006684:HLA-DR Antigens; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006389:Hemagglutinins, Viral; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell; D014759:Viral Envelope Proteins