Secondary MLC Responses of Primed Lymphocytes after Selective Sensitization to Non‐HLA‐D Determinants

Abstract

Two HLA-B,D-identical siblings, who differed only for the HLA-A region because of a maternal recombinational event, were studied in primary (1 degrees) and secondary (2 degrees) mixed lymphocyte culture (MLC). The HLA-A:B recombinant child did not respond to its HLA-B,D-identical sibling in either 1 degrees or 2 degrees MLC. In the reciprocal combination the non-recombinant child responded only weakly in 1 degrees MLC but responded significantly in 2 degrees MLC to the HLA-A:B recombinant child. Thus, it was possible to selectively prime to a non-HLA-D determinant, which is controlled by a gene located distal to HLA-B. Because this determinant was not present on T-cells, it could be distinguished from the serologically defined antigen controlled by the HLA-A locus. Such primed lymphocytes, as well as lymphocytes primed between HLA-identical siblings, revealed high autologous control responses which were not observed when using lymphocytes primed in conventional one-haplotype combinations. The significant 2 degrees MLC response to autologous cells after sensitization to allogeneic cells may reflect recognition of self antigens and raises the question to what extent genetic similarity between responding and stimulating cells is required in the priming phase to elicit a 2 degrees response to autologous cells.

DY determinants, possibly associated with novel class II molecules, stimulate autoreactive CD4+ T cells with suppressive activity.

“…DY-specific TCC displayed an unusual type of autoreactivity, being restimulated not only by autologous PBMC or B-LCL, but also by HLA-mismatched allogeneic cells. Using comparable priming conditions, similar reactivities in uncloned PLT cells have been noted previously (31), and, more recently, Martin et al . (32) have described possibly similar findings at the clonal level (32) .…”

“…They were found to proliferate in the presence of most stimulator cells, including PBMC from the autologous donor, GP (Fig. 7), as well as allogeneic PBMC and B-LCL (KR), and suppressive (29)(30)(31) but not helper (248-3) TCC. This is a pattern characteristic of "DY"-reactive cells.…”

Correlations between HLA‐D/DR associated Primed Lymphocyte Typing (PLT) defined DP‐antigens, HLA‐D and HLA‐DR antigens

“…Furthermore, it seems as if the PLT-technique may be a valuable tool both for the detection of heterogeneity between DP, HLA-D and HLA-DR antigens and for the identification of determinants not belonging to the series of HLA-D/DR associated DP-determinants (e.g. Wank et al 1978, Zier et al 1978, Morling et al 1980c, Shaw et al 1980, Termijtelen et al 1980).…”

HLA‐Linked Lymphocyte Activating Determinants

“…The class I loci. An HLA-A linked locus whose gene products are responsible for the induction of very weak responses in primary MLC was reported by Eijsvoogel et al (1972) and Bijnen et al (1977), whereas Wank et al (1979) confirmed the existence of such a locus and demonstrated its stimulating capacity in secondary MLC. Furthermore, it was suggested that a determinant encoded between HLA-A and -D/DR could induce weak stimulation in primary as well as secondary MLC (Wank et al 1977).…”