Molecular analysis of the variant alloantigen HLA-B27d (HLA-B*2703) identifies a unique single amino acid substitution.
HLA-B27 is a human major histocompatibility complex class I product defined by its antigenic specificity with conventional alloantisera. Detailed studies using monoclonal antibodies, cytotoxic T lymphocytes (CTL), and isoelectric focusing (IEF) gel electrophoresis demonstrated the heterogeneity in the B27 antigen. We have previously identified a unique variant molecule of B27 designated locally as B27d which is distinguished from other B27 variants by isoelectric point, serologic reactivity, and by a cloned CTL recognition. A gene encoding the B27d variant has been cloned and a complete nucleotide sequence has been determined. Compared to the sequence of the prototype B27a, the B27d has a single base substitution at codon 59 (B27a:TAT--B27d: CAT) in exon 2 responsible for Tyr to His substitution. A His residue at this position in the alpha 1 domain is unique among the known class I sequences and this single amino acid change is apparently sufficient to alter the epitope(s) recognized by antibody and cytotoxic T cell receptor. Previous primary structural analysis of the other five B27 variants has revealed differences of two to four amino acids. The combined structural data on the B27 variants indicate that (1) HLA-B27 represents a family of closely related B locus alleles that share the B27 allospecificity and differ by a limited number (one to four) of amino acid substitutions and (2) point mutation as well as gene conversion might be the mechanism responsible for the allelic variation of B27 antigen family.
Choo
S Y
SY
Puget Sound Blood Center, Fred Hutchinson Cancer Research Center, Seattle, WA 98104.
St John
T
T
Orr
H T
HT
Hansen
J A
JA
D000483:Alleles; D000911:Antibodies, Monoclonal / Q000276:immunology; D001483:Base Sequence; D003001:Cloning, Molecular; D005455:Fluorescent Antibody Technique; D006680:HLA Antigens / Q000235:genetics*; D015796:HLA-B27 Antigen; D006801:Humans; D007739:L Cells / Q000276:immunology*; D008969:Molecular Sequence Data; D014162:Transfection
D000911:Antibodies, Monoclonal; D006680:HLA Antigens; D015796:HLA-B27 Antigen