Promiscuous T-cell recognition of a rubella capsid protein epitope restricted by DRB1*0403 and DRB1*0901 molecules sharing an HLA DR supertype.
Two T cell clones derived from different donors with HLA-DRB1*0403 or DRB1*0901 phenotype recognize a rubella capsid peptide, C(265-273) in the context of several different HLA-DR molecules in addition to DRB1*0403 and DRB1*0901. All DR molecules restricting the T-cell clones have in common residues, R or Q at position beta 70, R at position beta 71, and E at position beta 74 in pocket '4' of the DR peptide binding groove, suggesting that a DR subregion structure or supertype, "Q/RRE" underlies the promiscuous T-cell recognition of this peptide. Single amino acid substituted analogs of peptide C(263-275) at anchor position 4 for natural residue R were tested for their ability to induce clonal T-cell cytotoxic responses. The results indicated that a positively charged residue, R or K, was required for T-cell recognition, suggesting a possible mechanism of electrostatic interactions between the negatively charged residue E at position beta 74 of these DR molecules and the positively charged residue at anchor position 4 of the peptide in T-cell recognition.
Ou
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Department of Paediatrics, Faculty of Medicine, University of British Columbia, Vancouver, Canada.
Mitchell
L A
LA
Décarie
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D
Tingle
A J
AJ
Nepom
G T
GT
D000595:Amino Acid Sequence; D000596:Amino Acids; D002213:Capsid / Q000138:chemical synthesis / Q000235:genetics / Q000276:immunology*; D002461:Cell Line, Transformed; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology*; D006684:HLA-DR Antigens / Q000276:immunology*; D059811:HLA-DRB1 Chains; D006801:Humans; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010455:Peptides / Q000138:chemical synthesis / Q000276:immunology*; D012412:Rubella virus / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000596:Amino Acids; D018984:Epitopes, T-Lymphocyte; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D010455:Peptides