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

Abstract

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.

Typing by cytotoxic lymphocytes. Genetics of HLA‐non‐A, B, C determinants—family studies

“…For a thorough account on the specificity of these clusters as judged from population data cf. and Kristensen (1978).…”

“…defining epitopes not recognized by available antibodies) on the basis of their ability to lyse T-lymphoblast panel target cells in the absence of any HLA-A, B, (C), sharing between stimulator and target cells. Previously published population studies which have used CTLs , Kristensen 1978 indicate that these CTLs form 3, possibly 4 clusters which may define separate traits. The clusters are negatively, albeit not significantly correlated, and the traits are in Hardy-Weinberg equilibrium.…”

“…In population studies the traits defined by these selected cytotoxic lymphocytes show a strong association to serologically defined HLA-antigens, indicating linkage as well as linkage disequilibrium to HLA, especially HLA-B (Kristensen 1978). These findings have by now been further challenged and confirmed in three European CML workshops (Kristensen 1978, Kristensen 1980. The objective of this communication is to elucidate the genetics of the target determinants recognized by Cytotoxic T-Lymphocytes (CTLs) using the CML technique and T-lymphoblasts (= PHA stimulated PBL) as target cells (cf.…”