A critical role for conserved residues in the cleft of HLA-A2 in presentation of a nonapeptide to T cells.
The peptide binding cleft of the class I human histocompatibility antigen, HLA-A2, contains conserved amino acid residues clustered in the two ends of the cleft in pockets A and F as well as polymorphic residues. The function of two conserved tyrosines in the A pocket was investigated by mutating them to phenylalanines and of a conserved tyrosine and threonine in the F pocket by mutating them to phenylalanine and valine, respectively. Presentation of influenza virus peptides and of intact virus to cytolytic T lymphocytes (CTLs) was then examined. The magnitude of the reduction seen by the mutation of the two tyrosines in the A pocket suggests that hydrogen bonds involving them have a critical function in the binding of the NH2-terminal NH3+ of the peptide nonamer and possibly of all bound peptide nonamers. In contrast, the mutations in the F pocket had no effect on CTL recognition.
Latron
F
F
Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115.
Pazmany
L
L
Morrison
J
J
Moots
R
R
Saper
M A
MA
McMichael
A
A
Strominger
J L
JL
D000595:Amino Acid Sequence; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D001665:Binding Sites; D002460:Cell Line; D003001:Cloning, Molecular; D000939:Epitopes / Q000276:immunology / Q000378:metabolism; D015789:HLA-A2 Antigen / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009980:Influenza A virus; D007700:Kinetics; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D009842:Oligopeptides / Q000276:immunology / Q000378:metabolism*; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014162:Transfection; D014764:Viral Proteins / Q000378:metabolism
D000939:Epitopes; D015789:HLA-A2 Antigen; D009842:Oligopeptides; D011994:Recombinant Proteins; D014764:Viral Proteins