Pohla, Heike and Kuon, W. and Tabaczewski, P. and Doerner, C. and Weiss, Elisabeth H.
Allelic variation in HLA-B and HLA-C sequences and the evolution of the HLA-B alleles.
In: Immunogenetics, Vol. 29: pp. 297-307
Several new HLA-B (B8, B51, Bw62)- and
HLA-C (Cw6, Cw7)-specific genes were isolated either as
genomic cosmid or cDNA clones to study the diversity
of HLA antigens. The allele specificities were identified
by sequence analysis in comparison with published HLAB
and -C sequences, by transfection experiments, and
Southern and northern blot analysis using oligonucleotide
probes. Comparison of the classical HLA-A, -B, and -C
sequences reveals that allele-specific substitutions seem
to be rare events. HLA-B51 codes only for one allelespecific
residue: arginine at position 81 located on the cd
helix, pointing toward the antigen binding site. HLA-B8
contains an acidic substitution in amino acid position 9
on the first central/3 sheet which might affect antigen binding
capacity, perhaps in combination with the rare
replacement at position 67 (F) on the Alpha-l helix. HLA-B8
shows greatest homology to HLA-Bw42, -Bw41, -B7, and
-Bw60 antigens, all of which lack the conserved restriction
sites Pst I at position 180 and Sac I at position 131.
Both sites associated with amino acid replacements seem
to be genetic markers of an evolutionary split of the HLA-B
alleles, which is also observed in the leader sequences.
HLA-Cw7 shows 98% sequence identity to the JY328
gene. In general, the HLA-C alleles display lower levels
of variability in the highly polymorphic regions of the Alpha 1
and Alpha 2 domains, and have more distinct patterns of locusspecific
residues in the transmembrane and cytoplasmic
domains. Thus we propose a more recent origin for the