Modulation of CD4+ T-cell recognition of influenza hemagglutinin by carbohydrate side chains located outside a T-cell determinant.
Two distinct T-cell clones raised to the H3 subtype influenza virus A/Memphis/71 fail to proliferate in response to other H3 viruses that contain the amino acid substitution Asp63-->Asn within the heavy (HA1) chain of the hemagglutinin (HA). These nonstimulatory viruses nevertheless have an intact sequence corresponding to the determinants recognized by the clones. The substitution at residue 63 results in the creation of a potential glycosylation site which occurs outside the boundaries of the T-cell determinants. A synthetic peptide encompassing the two determinants and extended to include residue Asn63 stimulated levels of proliferation of the clones similar to those obtained with a peptide containing Asp63. These results indicate that the presence of Asn rather than Asp does not in itself affect T-cell recognition. Partial enzymatic deglycosylation of isolated HA possessing the glycosylation site restored the ability of the T-cell clones to proliferate. More extensive deglycosylation of HA1 had a differential effect on the clones, allowing one to proliferate but not the other. These results illustrate that even when attached to residues outside a determinant, the carbohydrate of a glycoprotein antigen can influence T-cell recognition. In this way, changes in glycosylation patterns of HA from different isolates of the virus may influence the efficacy of preexisting T-cell immunity.
Drummer
H E
HE
Department of Microbiology, University of Melbourne, Parkville, Victoria, Australia.
Jackson
D C
DC
Brown
L E
LE
D000595:Amino Acid Sequence; D000818:Animals; D000918:Antibody Specificity; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D000939:Epitopes; D006023:Glycoproteins / Q000276:immunology; D006031:Glycosylation; D006389:Hemagglutinins, Viral / Q000276:immunology*; D009980:Influenza A virus / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000276:immunology; D013329:Structure-Activity Relationship
D000939:Epitopes; D006023:Glycoproteins; D006389:Hemagglutinins, Viral; D009842:Oligopeptides