The Complexity of the HL‐A Gene Product I: Study of a Serum Produced Against HL‐A5 in an HL‐A Semi‐Identical Situation

Abstract

A complex antibody developed in a W18 father immunized by his HL-A5 daughter was analysed. Four different antibodies appeared successively and were isolated by absorption and elution. These antibodies react directly or indirectly (CYNAP) with HL-A5, W21, W5, W17 and W15 cells. Some W21 cells are not reactive ( E T * ) ; some W5 cells are directly reactive, others only in CYNAP, which enables these two categories of cells to be subdivided.By absorption-inhibition, it was possible to demonstrate the existence of several determinants on the gene product, since the saturation of the absorbing cells by one antibody does not prevent the absorption of a second antibody (anti-HL-A5 and anti-[5, W21, W51). These distinct determinants or antigenic factors (Dausset et al. 1965) are shared by several allelic products. Their structures are probably similar since they are cross-reactive. Capping experiments indicate that all these determinants are borne by the same second locus molecule and are independent of the third locus molecule.The hypothesis that these shared and cross-reactive antigenic factors derived from each other by successive duplication and mutation of the corresponding gene is again emphasized.

The HLA‐B14 Cross‐Reactive Group

“…(Darke 1979). Legrand et al (1971) and Legrand & Dausset (1974) have, in addition, shown that determinants may be shared by more than two HLA antigens. I t seems probable, therefore, that the majority of the B14 complex antisera studied contain antibodies against many "shared determinants".…”

Cross‐Reactions of HLA Antibodies: VII. Rate of Sensitization and Serological Specificity

“…Interestingly, this study revealed the existence of subclasses of antibodies (clones) of varying specificity. Other studies, by Ahrons (1970), Grothaus and coworkers (1971) and more recently by Legrand & Dausset (1974) have shown that the absorption of HLA antibodies onto lymphocytes or platelets occurs within minutes. Since binding affinities varied from antigen to antigen, we questioned if the binding rates for specific or crossreactive antigens might differ sufficiently to allow a new and improved means of distinguishing primary from cross-reactivity.…”

“…The use of such sera has been limited by their "multispecificity" and often by an inability to determine which cytotoxic reactions are due to primary antibody specificity and which are due to cross-reactivity . Attempts to separate or define the antibody populations in crossreactive sera, notably by absorption and elution (Yunis et al 1972, Eguro et al 1973, Legrand & Dausset 1974, F(ab')z blocking (Richiardi et al 1973, Reisner et al 1976, Grumet et al isoantibodies. Later experiments by Dorf and coworkers (1972), using continuous pH gradient elution of an anti-HLA-A3 serum suggested that binding avidity between an antibody and homologous antigen is significantly greater than with crossreactive antigens.…”

A F(ab')2 fragment blocking study of the HLA‐B14 antigen

“…shared by several different allelic products , Legrand & Dausset 1973, 1974. The concept of shared or "public" determinants has been substantiated immunochemically (Schwartz et al 1979(Schwartz et al , 1980a(Schwartz et al , 1980b and by the use of monoclonal antibodies (Parham 1981, Parham & Brodsky 1981, Billing et al 1982, Ellis et al 1982, Haynes et al 1982).…”