The Bw4/Bw6 difference between HLA-B*0802 and HLA-B*0801 changes the peptides endogenously bound and the stimulation of alloreactive T cells.
HLA-B*0801 is unique among HLA-B allotypes in having dominant amino acid anchors at positions 3 and 5 of the peptide-binding motif. HLA-B*0802 is a variant of HLA-B*0801 in which the Bw6 sequence motif is replaced by a Bw4 sequence motif. This change, involving substitutions at positions 77, 80, 81, 82, and 83 of the B*08 heavy chain, is probably the result of a single evolutionary event of interallelic conversion. Moreover, the difference between B*0802 and B*0801 is sufficient to stimulate a cytotoxic T-cell response. To assess further the functional impact of the Bw4 motif on a B8 background, we compared the peptide-binding specificity of the B*0801 and B*0802 allotypes by sequencing the mixture of peptides endogenously bound to B*0802 and 12 individual peptides purified from that mixture. The HLA-B*0802 allotype, while able to bind some peptides bound by B*0801, has a broader repertoire of endogenously bound peptides than B*0801: the peptides bound by B*0802 are more variable in length and exhibit greater diversity in the carboxyl-terminal amino acid which interacts with the F pocket.
Arnett
K L
KL
Department of Structural Biology, Stanford University, Stanford, CA 94305, USA.
Huang
W
W
Valiante
N M
NM
Barber
L D
LD
Parham
P
P
D000595:Amino Acid Sequence; D002460:Cell Line; D015235:HLA-B Antigens / Q000737:chemistry* / Q000276:immunology; D006801:Humans; D008958:Models, Molecular; D011487:Protein Conformation; D013601:T-Lymphocytes / Q000276:immunology*; D014407:Tumor Cells, Cultured
D015235:HLA-B Antigens; C042388:HLA-Bw4 antigen; C038652:HLA-Bw6 antigen