DR3

Abstracts

i 7;$ possibility, we tested sera from 37 transplant patients ~26 retro and 1 | p r ~ J for antiidiotypic antibodies in the MLC test. Responder ¢transplant re¢ip/ent~ |ym~ phocytes were pretreated with autologous serum and rabbit C' before setting up MLC cultures. T h e antibodies inhibiting response:~ in MLC ¢¢ere dem~mmr~A~* in all recipients (n = 33) who had received BT. Such antibodies were not found in nontransfused patients (n = 4) and in normal subjects 01 = 5). Among transfu~d recipients, antibodies specifically inhibiting responses against antigens p r e ~ n t ~m the kidney donor were demonstrable in recipients (n = 18) with functional Miografts, but not in patients (n = 15) who had rejected the graft. For example, r g : ~ from a transplant patient (A3,11; Bw16,w35) with a functional graft from cadaver donor (A3,w3 ~;B 15,w44) inhibited responses to B15,Bw44 stimuL~ors. On the other hand, serum from transfused patient (A2,26;Bw44), who b~_l rejected renal allograft from a cadaver donor (A2,26;BI3,w44L did not inhib~, responses to B13 stimulators. Thus, specific antiidiotypic antibodkes were d,:monstrable in recipients with functional allografts, but not in patients who b~| rejected the graft. Also, this inhibition in MLC was seen only by pretreaemen, of responder cells, but not of stimulator cells. In a second series of experimems, responder lymphocytes were treated with serum for 2 hr and then added to MLC cultures. Addition of ser~tm-treated lymphocytes caused suppression o f certain MLC combinations, the specificity of which correlated with specificity obta/r~J in earlier series of experiments. Thus, the data suggest that antiidiotypic andbodies could be induced by blood transfusions and these antibodies may c ~ s ¢ generation of suppressor cells responsible for enhanced allograft su~'ival.

PLTs R E C O G N I Z I N G T W O DISTINCT DETERMINANTS, O N E I N D E P E N D E N T OF A N D T H E O T H E R RESTRICTED BY T H E SELF-HLA-DR. D.P. Singal I,. Fagnilli; ?dcMaster University, Hamilton, Ontario. Canada Six PLTs were generated between three HLA-A,B,C,DR ~AI,3:B8,w35: Cw4;DR3,5) identical unrelated individuals. These PLTs were tested for prJdferative respofises against stimulator lymphocytes from a selected panel o¢ 14 unrelated donors. Analysis of data showed a significant (r = 0.63, p
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Annual AACHT Meeting, 1982 with the self-DR antigen(s) and the other determinant, which is linked to HLA, is recognized independently of the roll-DR antigen.

PROLIFERATION OF ALLOANTIGEN-SENSITIZED HUMAN PERIPHERAL BLOOD LYMPHOCYTES BY AUTOLOGOUS LYMPHOCYTES ASSOCIATED WITH THE HLA-B8/DR3. D.P. Singal and L. F~0gnilli;McMaster University. Hamilton. Ontario. Canada In recent years, several investigators have shown that a proliferative response occurs when human T lymphocytes are stimulated in vitro by autologous non-T lymphocytes, in the present study we provide data which demonstrate that following in vitro sensitization to allogeneic lymphocytes in long-term MLC, primed PBL from HLA-BS/DR3-positive individuals respond significantly (p<0.0005) to autologous PBL in PLT. In experiments, where both responders and stimulators in long-term MLC were positive for HLA-B8,DR3-primed lymphocytes responded to autologous PBL ~mean SR = 8.44; range 3.50-22.69). In experiments, where PBL from B8,DR3-positive donors were primed against stimulating cells from BS,DR3-negative donors, primed lymphocytes again responded to autologous PBI gmean SR = 7.75; range 5.33-14.39). On the other hand, in experiments where PBL from B8,DR3-negative individuals were primed against stimulating cells from allogeneic donors, primed lymphocytes did not respond to autologous PBL ~mean SR = 1.62; range 0.92-2.76L No differences were observed when BS,DR3-negative lymphocytes were primed against B8,DR3negative (mean SR = 1.64; range 1.09-2.76) stimulators. Thus, the autoreactivity was dependent on the HLA type of the primed re,ponder lymphocytes. The possibility that inadequate inactivation of stimulators in primary long-term MLC contributed falsely u) autostimulation was eliminated by using the same stimulator lymphocytes u~ sensitize two different responders, one positive and the other negative for BS,DR3. This aumre~dvity was repr~t~cible and demonstrable at differer~t responder cell concentrations. The present data demonstrate that HLABS/DR3 alloantigens are a s ~ i a t e d with responsiveness to self-antigens and may thereby increase the likelihood of an aberrant immune response leading to the development of an autolmmune disease. ASSOCIATION OF HLA PHENOTYPE WITH INDIVIDUAL VARIATIONS IN FERRITIN SECRETION BY ACTIVATED HUMAN MONONUCLEAR (;~U.S. Maria de Sousa, Marilyn S. Pollack, Gwyneth Munn, Berta Martins da Silva, and bo Dupont; $1oan-Kettering In.~titlaefor CaJlcer Research. New York The study of ferritin secretion by human mononude~r cell, (MNC) is of interest because of increasing evidence that the immune system participates in the protection of potential tissue toxicity from iron, and ferritin is one of Ehe major proteins involved in iron transport and storage. We have recently shown that a modified hemolytic plaque-forming assay can be used to measure ferddn secretion by MNC in response to stimu~tion by PHA and ferric citrate. Since we observed that wide individual variations exist in the levels of ferridn secretion detected, as measured by numbers of plaque-forming cells, cells from 41 anrelated donors collectively representing all well-defined HLA-A,B,C and DR antigens were studied. "High" and "low" plaque-forming groulm were clearly distinguished as donors forming either > or < 3,000 plaque~/10 ~' cells, re~3,ectively. Analysis of the frequency of HLA antigens in the two groups ~owed a stati~ica|l~ significant