HLA-B37 and HLA-A2.1 molecules bind largely nonoverlapping sets of peptides.
T-cell recognition of peptides that are bound and presented by class I major histocompatibility complex molecules is highly specific. At present it is unclear what role class I peptide binding plays relative to T-cell receptor specificity in determination of immune recognition. A previous study from our group demonstrated that the HLA-A2.1 molecule could bind to 25% of the members of a panel of unrelated synthetic peptides as assessed by a functional peptide competition assay. To determine the peptide-binding specificity of another HLA class I molecule, we have examined the capacity of this panel of peptides to compete for the presentation of influenza virus nucleoprotein peptide NP-(335-350) by HLA-B37 to NP-peptide-specific HLA-B37-restricted cytotoxic T-lymphocyte lines. Forty-two percent of peptides tested were capable of inhibiting NP-(335-350) presentation by HLA-B37. Remarkably, none of these HLA-B37-binding peptides belong to the subset that was previously shown to bind to the HLA-A2.1 molecule. Only the NP-(335-350) peptide was capable of binding to both HLA-A2.1 and HLA-B37. These findings demonstrate that the peptide-binding specificities of HLA-B37 and HLA-A2.1 are largely nonoverlapping and suggest that, from the universe of peptides, individual HLA class I molecules can bind to clearly distinct subsets of these peptides.
Carreno
B M
BM
Molecular Immunology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892.
Anderson
R W
RW
Coligan
J E
JE
Biddison
W E
WE
D000328:Adult; D000595:Amino Acid Sequence; D001667:Binding, Competitive; D002478:Cells, Cultured; D015789:HLA-A2 Antigen / Q000235:genetics / Q000276:immunology*; D015235:HLA-B Antigens / Q000235:genetics / Q000276:immunology*; D059912:HLA-B37 Antigen; D006801:Humans; D007700:Kinetics; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis; D011485:Protein Binding; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D015789:HLA-A2 Antigen; D015235:HLA-B Antigens; D059912:HLA-B37 Antigen; D010455:Peptides