Allelic variations clustered in the antigen binding sites of HLA-Bw62 molecules.
HLA-Bw62 is a serologically defined class I antigen specificity, but we show that it represents a family of five distinct alleles in this study. Five variants of HLA-Bw62 antigens were identified by isoelectric focusing, and sequencing studies revealed that these are a family of closely related alleles differing from one another by one to six amino acid substitutions at eight positions: 63 in the alpha 1 domain and 94, 95, 97, 99, 113, 152, and 156 in the alpha 2 domain. These substitutions are located in the two alpha-helices and two adjacent beta-strands, and the side chains of most amino acids face into the antigen binding groove. Functional assays using an in vitro generated Epstein-Barr virus (EBV)-specific Bw62-restricted cytotoxic T lymphocyte clone indicated that the minimal structural variations located in the antigen binding sites of the HLA-Bw62 variant molecules could affect the presentation of the nominal EBV antigen. This study revealed that the HLA-Bw62 antigen family consists of at least five closely related alleles, and further demonstrated that these alleles with minimal structural variations might play distinct functional roles in regard to antigen presentation.
Choo
S Y
SY
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98104.
Fan
L A
LA
Hansen
J A
JA
D000483:Alleles; D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D004247:DNA; D015235:HLA-B Antigens / Q000737:chemistry / Q000235:genetics* / Q000276:immunology; D059910:HLA-B15 Antigen; D006801:Humans; D007525:Isoelectric Focusing; D008969:Molecular Sequence Data; D010641:Phenotype; D017434:Protein Structure, Tertiary; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D015235:HLA-B Antigens; D059910:HLA-B15 Antigen; C044141:HLA-Bw62; D004247:DNA