An Analysis of the Effect of Hla‐dp in the Mixed Lymphocyte Reaction

Abstract

SUMMARY It has recently been reported that HLA‐DP antigens may play an important role in the development of graft‐versus‐host disease (G VHD) following transplantation of haploidentical bone marrow as a treatment for haematological malignancies. Mixed lymphocyte culture (MLC) is routinely performed prior to bone marrow transplantation to assess the suitability of the donor, and we have therefore examined the role of HLA‐DP in this test. One‐way MLC chequerboard experiments were performed between 17 HLA‐Dw3 homozygous typing cells (HTC) with a range of HLA‐DP antigens represented, including HLA‐DPw1, w2, w3, w4 and CP63. The experiments were performed on multiple occasions and each time a highly significant difference (P= <0.001) was observed between the Relative Responses (RR) in the HLA‐DP matched responder/stimulator pairs and the HLA‐DP mismatched pairs. There was, however, considerable overlap in these results with ranges in the HLA‐DP‐matched group RRs of 0–17%, and 0–62% in the mismatched group. Only 3.1% of the HLA‐DP‐matched group had a RR>5%, while 48% of the HLA‐DP mismatched group had a RR>5%. From these results it was calculated that a positive response (> 5%) has a 96% chance of being due to an HLA‐DP disparity of one or two antigens. Conversely, with a negative MLC the chance of their being no HLA‐DP antigen disparity was only 65%. From these results we conclude, firstly, that HLA‐DP has a significant influence on the MLC. Secondly, it is clear that a negative MLC does not necessarily indicate identity at the HLA‐DP locus. An increased incidence of bone marrow transplants mismatched at HLA‐DP would be expected from increased use of phenotypically identical, but unrelated, donors and related donors sharing only one haplotype with the recipient. It would thus seem important to consider the HLA‐DP type of all patients and potential donors prior to bone marrow transplantation, since a negative MLC is not sufficient to eliminate HLA‐DP disparity.

HLA‐DP incompatibilities induce significant proliferation in primary mixed lymphocyte cultures in HLA‐A, ‐B, ‐DR and ‐DQ compatible individuals: Implications for allogeneic bone marrow transplantation

“…We found relatively little overlap in the range of the RRs in pairs with 0, 1 or 2 DP mismatches (Fig. 2), which is in contrast to the findings of Farrell et al (15).…”

“…This is in contrast to most previous studies in which homozygous typing cells of only a few Dw types have usually been investigated, i.e. Dw3 (15)(16)(17), DwlO (16) and Dw 18 (1 3). Isolated HLA-DP incompatibilities were found to induce strong proliferation in primary MLC with a mean RR of 42.5% (k27.2).…”

“…Isolated HLA-DP incompatibilities were found to induce strong proliferation in primary MLC with a mean RR of 42.5% (k27.2). Some (13,15,17) but not all (16) previous investigators have also found a significant, albeit less pronounced, effect of DP mismatches in primary MLC. Intriguingly enough, we observed that the RR was significantly influenced by the number of DP differences between responder and stimulator in a dose-dependent manner (Fig.…”

“…It is also reflected by the names first given to the DP antigens, secondary B-cell antigens (SB) by Shaw et al (1) and PL3A from primed lymphocyte antigen by Termijtelen et al (2). Subsequently, HLA-DP incompatibilities have been found to contribute to MLC reactivity in HLA-DR matched combinations (13,15). The influence of HLA-DP mismatches in primary MLC has also been documented in DP incompatible but otherwise HLA identical siblings from families with a DR-DQ/DP recombination.…”

“…In most previous studies the influence of HLA-DP incompatibilities in primary MLC has been investigated in homozygous typing cells (13,(15)(16)(17). We were interested in defining the stimulatory capacity of isolated HLA-DP mismatches in primary MLC performed with cells from HLA-A, -B, -DR and -DQ compatible, unrelated, heterozygous individuals.…”