Two Separate Genes Controlling Stimulation in Mixed Lymphocyte Reaction in Man

Abstract

The genetic control of strong stimulation in the mixed lymphocyte culture reaction is determined by a separate gene (MLR-S) Recent findings show that the genetic control of stimulation in the mixed lymphocyte culture (MLC) reaction in man is determined by a separate gene (MLR-S) closely linked to the FOUR-locus of the HL-A chromosomal region (1). This gene must be located outside the 1IL-A chromosomal region as indicated by studies of the AILC-reactions within families with recombinations of the major histocompatibility region (MlHlR) between the FOUR-locus and the MILR-S locus (1-8).In this study we present data on three recombinant children with recombination between the FOUR-locus and the MLR-S locus in two families. The MLC data from these families confirms the hypothesis that the MLR-S locus is located outside the HL-A chromosomal region. An analysis of normal material of zero, one, and two iHL-A haplotype different combinations has made it possible to evaluate the MLC results obtained in the HL-A haploidentical, MLR-S identical combinations. This has clarified that more than one gene is responsible for the stimulation in the MLC test. It is concluded, that the MLR-S locus is responsible for a strong allogenie cell stimulation, while one or more genes located within the ilL-A chromosomal region may contribute with a weak Abbreviations: MILC, mixed lymphocyte culture; S1R, stimulation rates; AMiR, major histocompatibility region; SCII), severe (Table 1 and Fig. 1). A total of 479 of these tests represented unrelated IIL-A nonidentical, two-haplotype different combinations, 127 were haploidentical siblings or parent-child combinations, while the remaining 52 tests were performed between HL-A identical siblings. Calculations of the data obtained withiii each of the three groups were based on logratios. The log-value for mean, SD, SE of mean, was determined and the log-ratios were retransformed into simple ratios for further analysis. One family (Minnesota family BR) (

Mixed lymphocyte cultures in rheumatoid arthritis.

“…One hypothesis was that it reflects an abnormality in the function of lymphocytes or of phagocytic cells and therefore perhaps manifestation of a defect of cellular immunity associated with pathogenesis of the disease (8). Reactions in MLCs are known to result from recognition of the lymphocytedefined (LD) histocompatibility determinants which are products of loci close to, but separate from the A (LA), B (Four), and C (AJ) loci of the HLA region, (9)(10)(11), Typing for these determinants is now made possible through the use of LD homozygous MLC-typing cells (12)(13)(14)(15). In the present work methods commonly used in histocompatibility studies were applied to the investigation of MLC reactions of lymphocytes in patients with RA.…”

At Least Two Loci of the Major Histocompatibility Complex Can Determine Mixed Lymphocyte Stimulation in the Rat

“…1973, Klein et al 1972, Widmer et al 1973, for man (Eijsvoogel et al 1972, Mempel e t al. 1973, Dupont et al 1974, rhesus monkey (Balner 1977), and dog (Bijnen et al 1977).…”

Protection of Lethally Irradiated Mice by Spleen Cells from Neonatally Thymectomized Mice

“…These findings seem to us highly relevant to efforts to treat severe combined immunodeficiency in man by bone-marrow grafting of unrelated individuals. From our studies, one might predict that giving populations of cells deficient in differentiated post-thymic cells and rich in undifferentiated post-thymic cells or a mixture of undifferentiated post-thymic and prethymic cells may be most useful in the treatment of severe combined immunodeficiency diseases in man when an HLA-MLR-S identical sibling or an MLR-S match of a family member or an MLR-S match from the general population is not available as a donor (13)(14)(15). Indeed, it is quite possible that a fetal liver transplant, which may have corrected the immunodeficiency of one child with severe combined immunodeficiency disease and adenosine deaminase deficiency without producing serious graft-versus-host reaction as reported by Keightly et al (personal communication), may be an example of this principle in operation.…”

“…Groups of 20 mice of 10-to 15-day-old and 35-to 45-day-old thymectomized or nonthymectomized mice of Af, C3Hf, or (C3Hf X Af)F1 strains were used as donors. Mice of 3 months of age received either 550 or 750 exposure to irradiation (220 kV, 15 mA, 0.25-mm copper filter and 1 mm of aluminum, target distance of 60 cm, halfvalue layer of 0.98 mm of copper). The exposure values corrected for backscatter factor and converted into dose would be 767 rads and 1046 rads.…”