ALLORESPONSES TO HLA-DP DETECTED IN THE PRIMARY MLR - CORRELATION WITH A SINGLE AMINO-ACID DIFFERENCE

The one-way mixed lymphocyte reaction (MLR-1) response was measured in both directions in 50 HLA-A, B, DR and DQ identical pairs and the rol e of DP studied in MLR stimulation. DR, DQ and DP typing was performed at the allele level by the polymerase chain reaction-sequence specifi c oligotyping (PCR-SSO) technique. The group consisted of 19 potential bone marrow transplant recipients and 34 marched unrelated donors. Wh en more than one matched donor was available for a patient, donor/dono r MLR-1 was also studied. DP identity was observed in 3 out of 50 pair s (6%), however due to homozygosity no incompatibility was present in the stimulating cells in 21 out of 100 cases (21%). There was a signif icant difference in the range of relative responses (RR) between zero DPB1 mismatches and one (p = 0.002) and two (p = 0.02) DPB1 mismatches : 52.4% of cases in the zero DPB1 mismatch group had RR < 1.0% compare d with 31.6% and 27.3% in the one and two DPB1 mismatches. Stimulation by DPB10201 and 0301 gave the highest RR (12.9 +/- 22.5 and 17.5 +/- 17.0, respectively) while stimulation with DPB10401 and 0402 resulte d in low levels of T cell response (1.3 +/- 8.2 and 0.6 +/- 11.5, resp ectively). When the responses were restricted to DPB10401 homozygotes to standardise for responder type similar results were obtained (DPB1 0201 v DPB1*0402 p = 0.008). The protein products of the DPB1*0201 an d 0402 alleles differ by a single amino acid at position 69 (DPB10402 -Lysine, DPB10201-glutamic acid). A further analysis was performed th erefore scoring responders and stimulators as glutamic acid positive ( E+) or negative (E-). There was a highly significant increase in the r esponse to E+ stimulators compared with E- stimulators (p = 0.004). Th ere was also a significant difference in the distribution of relative responses between the E+ stimulator group and the subgroups of E- resp onders/E-stimulators (p = 0.012) and E+ responders/E- stimulators (p = 0.009). However the amino acid difference at position 69 does not exp lain all responses due to DP in the MLR-1 as evidenced by the strong r esponses observed in cases where DPB10301 (lysine pos.) was the only difference on the stimulator cells. The results indicate that not all DP incompatibilities elicit a measurable T cell MLR response, but wher e a response does occur residue 69 in the first domain of DP appears t o be pivocal. These results may have implications with respect to GVHD in bone marrow transplantation. (C) American Society for Histocompati bility and Immunogenetics, 1997. Published by Elsevier Science Inc.