HLA-A,B,C and haplotype frequencies in the Finnish population.
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Biomedical subjects
Publications and source records attributed to M Julin.
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The prevalence of histocompatibility antigen HLA-Cw6 was 72.7% in twenty-two patients with the guttate form and 45.9% in thirty-seven patients with the vulgaris form of psoriasis; the difference between these figures and the prevalence (7.4%) in 462 healthy blood donors in Finland is highly significant. The previously observed excess of several HLA-B locus genes might be secondary to their close linkage with the Cw6 gene. Hereditary factors appear more important in the guttate than in the vulgaris form of psoriasis.
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Mice of 10 inbred strains were immunized with a protein conjugate of a hapten of p-azobenzenearsonate coupled to the carbon atom 5 of hydroxphenylacetic acid (ABA-HOP), and anti-ABA-HOP titers were determined by the haptenated phage inactivation. Mean titers of C57BL/6 and BALB/c mice were significantly lower than those of A/J and CBA strains. The titers were under a polygenic control and did not correlate with allotypes in backcross mice. Fine specificity of the anti-ABA-HOP was characterized by inhibiting the haptenated phage inactivation reaction with five chemically related compounds including ABA-HOP (Fig. 1). This antibody was genetically more polymorphic than any other antibody studied. Three distinct idiotypes could be demonstrated and the number is probably greater. The idiotypes of the A/J and C57BL/6 were inherited as allotype-linked dominant Mendelian traits, the former in two and the latter in three different backcrosses. Condominance of the two alleles was shown since approximately equal amounts of the two idiotypes were produced by the population of heterozygous mice. There were many individual heterozygotes, however, in which only one parental idiotype could be detected. In other individuals of the same genotype the other parental idiotype was predominant. In many mice a mixture of the two idiotypes was indicated by doubly sigmoid inhibition curves. The causes for the variation in the expression of the two alleles in genotypically identical mice is discussed.
Characteristics (titre and fine-specificity) of natural anti-NP antibodies were determined in eighteen inbred strains of mice. We found systematic titre and fine-specificity differences between different strains. At least five types of strains could be easily detected but the data indicate that the actual number is greater. Strains sharing an Ig allotype tended to have less different anti-NP antibodies than those not sharing the allotype. Fine-specificity of natural anti-NP antibodies resembled fine-specificity characteristics in immune anti-NP antibodies of the same strains. Both are probably controlled by V genes. The data indicate that fine-specificity of antibodies has a great resolving power in the study of Mendelian V genes.
Our earlier work had demonstrated a fine-specificity idiotype in anti-NP antibodies of C57Bl/6 mice. It was controlled by a VH gene (VH-NPb). The idiotype could be demonstrated in all anti-NP of the C50Bl/6 mice (IgG, IgA, IgM including natural anti-NP). The VH-NPb gene is condominant with CBA allele F1 hybrid mice in the production of natural antibodies but dominant over the CBA allele in immune antibody formation (92% of F1 mice were like C57Bl/6). Probably the product of this gene has a higher affinity for NP than the average affinity of idiotype-negative antibody in the F1 hybrids. Both the codominance in natural antibodies and the dominance in immune antibodies had the peculiar characteristic that genotypically identical individuals varied a great deal. The share of idiotype-positive antibody in the total natural anti-NP titre of (C57Bl/6 x CBA)F1 mice varied from less than 33% to more than 67%. In immune antibodies individual differences were still greater, in ca 92% of mice only idiotype-positive anti-NP could be detected and in ca 8% only idiotype-negative antibody was detectable. Only few F1 hybrid mice had detectable amounts of both types. Homozygous mice of the LP strain behaved in all aspects like the F1 mice. Of their natural anti-NP titres 50% were due to idiotype-positive antibody and in the immune antibodies the figure was 86%. Individual non-immune sera again contained varying mixtures of idiotype-positive and idiotype-negative antibody, but immune sera contained only one or the other type. The third allotype b strain tested, C57Bl/Ka, took an intermediary position between LP and C57Bl/6. Ca 70% of natural anti-NP titres were due to idiotype-positive antibody but all immune anti-NP was idiotype-positive.