K. N. Stewart

THE FETUS AS AN ALLOGRAFT: EVIDENCE FOR PROTECTIVE ANTIBODIES TO HLA-LINKED PATERNAL ANTIGENS

Non-cytotoxic antibodies to paternal B lymphocytes were detected in sera from 11 of 11 multiparous women and from 11 of 16 normal primigravidae during the first trimester of pregnancy. These antibodies were not, however, detected in sera from 9 of 10 women of comparable gestation at the time of spontaneous abortion. By means of a rosette inhibition assay, the difference in antibody activity between the primigravidae (mean 37.9 +/- 19%, median 36.5%) and the women subject to spontaneous abortion (mean 7.3 +/- 11.6%, median 0%) was statistically significant. This antibody activity was not directed to the known HLA specificities (HLA--A, B, C, or DR), but linkage to the HLA gene complex was suggested by family studies. These results provide evidence for an HLA-linked antigen system not defined by conventional tissue-typing techniques. Fetomaternal disparity at this antigenic site may be important for successful pregnancy.

Identification of subpopulations of T lymphocytes and Ia positive B lymphocytes using a rosette assay based upon the biotin-avidin interaction

Bovine erythrocytes were coated with avidin using a chromic chloride coupling technique and used successfully in an indirect rosette assay to identify and quantitate: (a) T-lymphocyte helper and suppressor subpopulations, and (b) Ia positive B-lymphocyte populations. Using mouse monoclonal antibodies to the T-lymphocyte markers OKT3, OKT4, and OKT8 it was shown that the proportion of OKT4 and OKT8 positive cells were respectively 60.9 and 39.2% of the total OKT-3 positive T lymphocytes. In a similar way, using a monoclonal anti-human Ia antibody, the percentage Ia positive cells in B-lymphocyte enriched preparations was shown to vary between 18 and 55% for normal peripheral blood and 31 and 58% for chronic lymphocytic leukaemia derived peripheral blood.

Non-cytotoxic alloantibodies defined by the EA rosette inhibition assay.

Sera from both transfused individuals and pregnant women mediated inhibition of Fc-rosette formation. Both normal blood B lymphocytes and chronic lymphocytic leukemia cells were used as targets. Inhibition was not related to the presence or absence of lymphocytotoxic antibodies. When tested against a panel of B lymphocytes these sera displayed selective reactivity in keeping with the recognition of allospecific determinants. No association between the target antigen(s) and classically defined MHC-coded structures was evident. Heteroantibodies to both class I and class II MHC structures as well as beta 2-microglobulin also mediated FcR blockade. However, unlike the alloantisera tested, these antibodies displayed no restriction in their reactivity toward individual target cells.