An HLA-A2 population variant with structural polymorphism in the alpha 3 region.
The HLA-A2 antigen expressed by donor OZB can be distinguished from the main HLA-A2.1 subtype by isoelectric focusing - it is one charge unit more acidic - and by some alloreactive T-cell clones but not by cytolytic T lymphocyte lines. The structure of variant OZB has been examined by comparative peptide mapping with A2.1 and radiochemical sequence analysis. The two molecules were found to differ in a single tryptic peptide from the alpha 3 region, spanning residues 220-243. The amino acid sequence of this peptide from variant OZB revealed that there was only one amino acid change of Glu instead of Ala at position 236, a hitherto invariant residue in class I HLA antigens. All previously characterized HLA or H-2 natural variants have structural changes restricted to the alpha 1 and/or alpha 2 domains. Thus, variant OZB is unique in that (1) it has one amino acid change in alpha 3 and (2) it has no changes in alpha 1 and alpha 2. The only detected substitution of this variant may be accounted for by a single base change at the DNA level, suggesting that it might have resulted from a point mutation in the A2.1 gene. The structural features of variant OZB open a novel way to examine the influence of polymorphism in alpha 3 on cytolytic T-cell recognition of naturally occurring class I antigens.
Castaño
R
R
Department of Immunology, Fundación Jiménez Díaz, Consejo Superior de Investigaciones Científicas, Madrid, Spain.
Ezquerra
A
A
Doménech
N
N
López de Castro
J A
JA
D000595:Amino Acid Sequence; D002851:Chromatography, High Pressure Liquid; D014644:Genetic Variation; D006680:HLA Antigens / Q000235:genetics*; D015789:HLA-A2 Antigen; D006801:Humans; D007525:Isoelectric Focusing; D008969:Molecular Sequence Data; D010449:Peptide Mapping; D013601:T-Lymphocytes / Q000276:immunology
D006680:HLA Antigens; D015789:HLA-A2 Antigen