Characterization of the HLA-restrictive elements of a rubella virus-specific cytotoxic T cell clone: influence of HLA-DR4 beta chain residue 74 polymorphism on antigenic peptide-T cell interaction.
The influence of glutamic acid (E)-alanine (A) dimorphism at position 74 of the DR4 beta chain on cytotoxic T cell recognition of an antigenic rubella virus peptide, E1(273-284), was studied using a panel of B cell lines and B cell transfectants expressing different HLA-DRB1 alleles as antigen-presenting cells and targets in 51Cr-release assays. Only B cell lines expressing the DRB1*0403, DRB1*0406 or DRB1*0407 subtypes which shared a residue, E, at position 74 in the DR4 beta chain when sensitized with E1(273-284) elicited strong cytotoxic T lymphocyte responses. However, in direct binding and antibody inhibition assays, it was shown that biotinylated E1(272-285) could bind to DR molecules with residues other than E at position 74, including DRB1*0401, DRB1*0404 and DRB1*1101 expressed on transfectants. E1(272-285) bound with similar affinity to the transfectant with DRB1*0403, which has E at position 74, as well as the transfectant with DRB1*0404, which does not. When T-B cell engagement rates were compared in cell conjugate assays, the percentage of T-B conjugates was higher when peptide-pulsed transfectants with DRB1*0403 were used than with transfectants expressing DRB1*0404. Hence, the HLA DR beta 1 polymorphism at position 74, while not critical for the binding affinity of E1(272-285) to the HLA molecule, appears to be a primary determinant of restricted recognition and subsequent activation of the peptide-specific T cells.
Ou
D
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Department of Paediatrics, Faculty of Medicine, Children's Hospital, University of British Columbia, Vancouver, Canada.
Mitchell
L A
LA
Domeier
M E
ME
Tsang
A O
AO
Décarie
D
D
Tingle
A J
AJ
Nepom
G T
GT
Lacroix
M
M
Zrein
M
M
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000276:immunology*; D000956:Antigens, Viral / Q000276:immunology*; D002999:Clone Cells; D006680:HLA Antigens / Q000235:genetics*; D015804:HLA-DR4 Antigen / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D010455:Peptides / Q000276:immunology*; D012412:Rubella virus / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000596:Amino Acids; D000956:Antigens, Viral; D006680:HLA Antigens; D015804:HLA-DR4 Antigen; D010455:Peptides