Cell Mediated Lympholysis in Man: An Attempt to Type with Cytotoxic Lymphocytes

Abstract

From approximately 3000 CML [cell mediated lympholysis] combinations, originally established to evaluate the qualitative and quantitative influence of the serologically defined HL-A-A, B and C antigens on cellular, complement independent cytolysis, 12 combinations were selected yielding reproducible positive cytolysis on allogenic target cells, although no HL-A-antigenic sharing could be demonstrated between stimulator and target lymphocytes. These 12 cytotoxic lymphocytes (CTL) were tested in parallel as CML typing combinations against lymphocytes from a random population sample of 100 unrelated Danes. Based on a pairwise analysis, 11 of these CTL could be classified into 2 groups of significantly correlated CTL. These 2 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 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 HL-A-A, B, C or D antigens may be targets for destruction. This study suggests that known HL-A antigens are not sole target determinants in CML or that cytotoxic lymphocytes recognize HL-A 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 HL-A region. Cytotoxic lymphocytes may recognize backbone structures of the HL-A molecules.