Escape from Sensitization to HL‐A Antibodies

Abstract

Human lymphocytes sensitized with HL‐A antibodies could not be killed by the addition of complement if the lymphocytes were incubated for periods of 1 to 5 hours at 37° C. This phenomenon was not produced by simple dissociation of the antibodies or by loss of antigens (modulation), but rather is postulated to result from an active release or pinocytosis of HL‐A antigens together with the attached antibody. “Escape from sensitization” is followed closely by reformation of antigens, for the cells can readily be resensitized and killed by addition of complement. Loss of sensitization is an active process, since one‐day‐aged lymphocytes or lymphocytes treated with actinomycin D or puromycin were unable to express this activity. A differential escape rate for different specificities was encountered indicating that HL‐A9 was produced more rapidly than several other specificities present on the same lymphocytes. A correlation was noted between the rate of HL‐A antigen synthesis by lymphocytes (indicated by escape rate) and the quantity of HL‐A antigen in the serum. Inhibition of lymphocyte cytotoxicity was used to detect the presence of HL‐A antigens in serum. Certain specificities, such as HL‐A9, were generally present in serum whereas others, such as HL‐A8, could not be detected. Cross‐inhibition tests with over 100 sera clearly showed an association of inhibition with specificity, although nonspecific inhibition was often observed. Sephadex fractions of sera tested at different concentrations revealed the greatest inhibitory activity in the 19S and 7S fractions.

Modulation of the H‐2 Antigenicity on the Surface of Murine Peritoneal Cells

“…Loss of sensitivity to C' occurred upon incubation for several hours at 37' C but not at 0' C, and was prevented by actinomycin D. This phenomenon was shown to reflect, at least in part, the elution of antibody from the surface of antibody-coated cells (Chang et al 1971). A similar phenomenon of '<escape from sensitization" was recently described by Miyajima et al (1972) for human lymphocytes. Peripheral blood lymphocytes, coated with HL-A antibodies and incubated at 37' C in antibody-free medium, lost their sensitivity to lysis upon addition of C'.…”

An Initial Investigation of Lymphocyte Antibody Activity through Pregnancy and in Eluates Prepared from Placental Material

“…Since no significant excess amount of antibody activity has been found in the eluates, the possibility arises that antigedantibody complexes are removed from the placental surface once combination has taken place. The process of LLescape from sensitization" is evidence for this (Miyajima et al 1972). A logical progression would then allow for further HL-A antigens to be produced on the placental surface, thus preventing eventual swamping of the placenta by antibody which would culminate in antibody reaching the foetal circulation.…”

The Reactivtiy of Leukaemic Cells to HL‐A Typing Sera

“…We have noted, however, that in prospective kidney donors receiving large doses of steroids, typing is impossible and no positive reactions have been obtained until the cells have been held for some hours following separation. In this situation, the drugs used seem to have removed the antigens of the cell membrane, since the period of recovery coincides with the time for antigenic turnover observed in experiments on escape from sensitisation (Miyajima et al 1972).…”