Alloreactive cytotoxic T-lymphocyte-defined HLA-B7 subtypes differ in peptide antigen presentation.
We investigated T-cell-defined HLA-B7 subtypes using cDNA sequencing, analysis of bound peptides, and reactivity with a panel of alloreactive cytotoxic T-lymphocyte (CTL) clones. Three subtypes (HLA-B*0702, HLA-B*0703, and HLA-B*0705) differ in nucleotide and predicted amino acid sequence. CTL reactivity and pooled peptide sequencing show that these three HLA-B7 subtypes bind distinct but overlapping sets of peptides. In particular B*0702 expresses D pocket residue Asp 114 and binds peptides with P3 Arg, whereas B*0705 expresses D pocket residue Asn 114 and binds peptides with P3 Ala, Leu, and Met. Consistent with different peptide-binding specificities, three alloreactive CTL differentiate between cells expressing B*0702, B*0703, and B*0705 by detecting specific peptide/HLA-B7 complexes. In contrast, three other T-cell-defined HLA-B7 subtypes are identical to HLA-B*0702. The B*0702-expressing cell lines are differentiated by two of ten CTL clones. One CTL clone differentiates B*0702-expressing cells by their ability to present peptide antigen. Thus differences in peptide presentation can explain differential CTL recognition of cell lines expressing structurally identical and variant HLA-B7.
Smith
K D
KD
Department of Pathology, University of Iowa College of Medicine, Iowa City 52242, USA.
Epperson
D F
DF
Lutz
C T
CT
D000595:Amino Acid Sequence; D017951:Antigen Presentation; D001483:Base Sequence; D018968:CD58 Antigens / Q000096:biosynthesis; D018076:DNA, Complementary / Q000235:genetics; D005805:Genes, MHC Class I; D015793:HLA-B7 Antigen / Q000096:biosynthesis / Q000737:chemistry / Q000145:classification / Q000235:genetics / Q000276:immunology*; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology*; D011487:Protein Conformation; D016415:Sequence Alignment; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D018968:CD58 Antigens; D018076:DNA, Complementary; D015793:HLA-B7 Antigen; D010446:Peptide Fragments; D018799:Intercellular Adhesion Molecule-1