In a family with a large pericentric inversion in one chromosome No. 6 (Inv(6)(p+q–)), HL-A was shown to have segregated with this chromosome in seven of seven cases. This raises the probability for the localization of HL-A to chromosome No. 6 from a prior 6 to 49 % and confirms the same assignment reported from cell hybridization work. The HL-A locus is most likely to be a little distal to the midpoint of either the short or the long arm of chromosome No. 6.
In 107 matings with 377 children studied in this report the acid phosphatase distribution is in accordance with a three allele hypothesis. This is also found when the results of all the family studies made up ta the present are compiled. A family is presented in which the Pd allele is shown to be segregating at the AcP locus. The gene frequencies in Denmark are: Pa: 0.353; Pb: 0.591; Pc: 0.055 and Pd: 0.0007.
From approximately 3,000 CML combinations, originally established in order to evaluate the qualitative and quantitative influence of the serologically defined HLA‐A, B, and C antigens on cellular, complement independent cytolysis, 12 combinations were selected yielding reproducible positive cytolysis on allogenic target cells, although no HLA‐antigenic sharing could be demonstrated between stimulator and targeTlymphocytes.
These 12 CytoToxic Lymphocytes (CTL's) have been tested in parallell as “CML typing combinations” againsTlymphocytes from a random population sample of 100 unrelated Danes. Based on a pairwise analysis 11 of these CTL's could be classified into two groups of significantly ‘ correlated CTL's. These two groups do not define monospecific traits of allelic genetic origin as judged by a mutually positive correlation and a poor fit to Hardy‐Weinberg equilibrium. The traits defined by these groups may be either partially identical or governed by closely linked loci. The same groups were identified and the same conclusions reached after exclusion of those individuals in the population sample where HLA‐A, B, C, or D antigens may be targets for destruction.
Thus, this study gives direct evidence that known HLA antigens are not sole target determinants in CML or that cytotoxic lymphocytes recognize HLA molecules in a different way than lymphocytotoxic antibodies. The studies underline the immunogenetic complexity of CML although this reaction is most probably governed by genes in the HLA region. It is suggested that cytotoxic lymphocytes may recognize “backbone structures”; of the HLA molecules.
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