Do antigenic drift residues in influenza hemagglutinins of the H3 subtype qualify as contact sites for MHC class II interaction?
We have previously reported that a majority of hemagglutinin-specific and class II (Ak or Ad)-restricted T cell clones, elicited by natural infection with X31 virus (H3N2 subtype), focus on regions of the HA1 subunit that have featured in antigenic drift and exhibit extensive diversity in their ability to discriminate between variant viruses with amino acid substitutions in these sites. The structural basis for the loss of recognition of a major antigenic site, HA1 120-139, was investigated by (i) comparing the effects of amino acid substitutions in mutant hemagglutinins (HA1 129 Gly----Glu; 132 Gln----Glu; 135 Gly----Arg) with the corresponding substitutions in synthetic peptides or (ii) by assessing the effects of single amino acid substitutions (to Ala) in the alpha k chain (residues 50-79) on the ability of Ak transfectants to present peptides. Despite the failure to recognise mutant viruses, mutant peptides were recognised as efficiently as wild-type peptides in association with wild-type Ak. However, the mutant Ak transfectants identified a different set of alpha k residues (positions 56, 65, and 72) as being critical for presentation of mutant peptides. Taken together with our previous findings that defects in antigen presentation of mutant hemagglutinin are reversed by single substitutions in the alpha k chain (residues 56 and 62), it would seem that the antigenic drift residues in mutant hemagglutinins alter the profile of contact sites with class II.
National Institute for Medical Research, Mill Hill, London, UK.
C M
CM
Graham
A P
AP
Warren
D B
DB
Thomas
D000595:Amino Acid Sequence; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D000956:Antigens, Viral / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002999:Clone Cells; D006389:Hemagglutinins, Viral / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D009980:Influenza A virus / Q000276:immunology*; D051379:Mice; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D011485:Protein Binding; D013329:Structure-Activity Relationship; D014162:Transfection
D000956:Antigens, Viral; D006389:Hemagglutinins, Viral; D000949:Histocompatibility Antigens Class II; D010455:Peptides