Complementation and Serological Analysis of an H-2 Mutant1

Widmer

The Journal of Experimental Medicine

et al. 1972

272

The mixed leukocyte culture (MLC) t test has been used as a measure of histocompatibility and as a model of the recognition phase of the homograft reaction. Studies in man (I), mouse (2), and rat (3) have suggested that activation or stimulation in MLC is dependent on differences at the major histocompatibility complex (MHC) although exceptions to this rule have been found (4). In the mouse the MHC includes two serologically defined (SD) loci, H-2K and H-2D, immune response (Ir) loci (5, 6), loci governing susceptibility or resistance to tumor viruses (7), and the Ss-Slp loci (8).It was naturally assumed that since MLC activation was dependent on MHC differences, SD antigen differences were responsible for stimulation. Unusual and aberrant cases in human studies (9-12) suggested, however, that in addition to the SD loci, there may be MHC differences which are difficult to detect serologically using the usual methods of immunization and testing, but which can cause a lymphocyte proliferative response. We will refer to such differences as lymphocyte-defined (LD) differences (13).We will present data in this paper which we have obtained in mouse MLC studies. We have for the most part made use of congenic strains of animals carrying recombinant M H C chromosomes (strains that are genetically identical except for the genes of the MHC). This allows us to test two animals differing for only some segment of the MHC. In a few cases we have studied animals differing for the M H C and for loci segregating independently of the M H C ; these will be discussed in detail. Our results indicate that the strongest MLC activation is associated with Ir

Section: Discussionsupporting

confidence: 89%

Serologically Defined and Lymphocyte-Defined Components of the Major Histocompatibility Complex in the Mouse

Widmer

The Journal of Experimental Medicine

et al. 1972

272

The Journal of Experimental Medicine

“…The mutant H-2 ~a and H-2 ~I haplotypes of the B6.C-H-2 ~ By (B6-H-2 ~a) and B6.C-H-2 bl By (B6-H-2 #~) mice were discovered by Bailey and Kohn through reciprocal circle grafting analyses designed to identify histocompatibility (H) gene mutations (17). Complementation tests demonstrafed that both mutations occurred in the K end of the H-2 ~ haplotype (18,19). Reciprocal, primary MLC of B6-H-2 ~ and B6.H-2 br lymphocytes and B6 lymphocytes result in responder proliferation (14,19).…”

Section: Methodsmentioning

confidence: 99%

T-lymphocyte response to H-2 mutants. I. Proliferation is dependent on Ly 1+2+ cells.

Wettstein¹,

Bailey²,

Mobraaten³

et al. 1978

We have determined the Ly phenotype of the T lymphocytes which proliferate in response to mutant H-2K and H-2D alloantigens in primary mixed lymphocyte culture. Responder T cells proliferating in reciprocal cultures of H-2d(KdDd) and H-2da(KdDda) lymphocytes were typed Ly 2+ through selective depletion with specific alloantiserum plus complement. Further, B6-Ly 1a lymphocytes proliferating in response to B6-H-2ba and B6-H-2bf stimulators were typed as Ly 1+2+ through similar analysis. These results are discussed with regard to their impact on views of lymphocyte differentiation and factors determining the identity of alloreactive lymphocytes.

Clinical and Experimental Immunology

“…C57BL/6 (B6); B6.C-H-2bmJ (bm1), H-2K mutant strain (Bailey, Snell & Cherry, 1971); and B6.C-H-2bmJ2 (bml2), I-A mutant strain (McKenzie et al, 1979) were originally from the Jackson Laboratory, Bar Harbor, ME. BlO.Thy-1.1, Thy-1 congenic strain (Muto et al, 1983) was kindly provided by Dr T. Sado, Division of Physiology and Pathology, National Institute of Radiological Science, Chiba, Japan.…”

Section: Materials and Methods Micementioning

confidence: 99%

“…There have been several reports (Rappaport et al, 1979;Jaffee & Claman, 1983;Charley et al, 1983;Piquet et al, 1987) describing cutaneous lesions in murine systemic GVHD. In spite of the disadvantage that lethal irradiation itself might induce the epidermal cell damage, cutaneous lesions of systemic GVHD were induced in lethally irradiated mice after reconstitution with donor type bone marrow cells, probably because it is difficult to reproduce cutaneous lesions in the murine systemic GVHD system without lethal irradiation.…”

Section: Introductionmentioning

confidence: 99%

Induction of cutaneousgraft-versus-hostdisease by local injection of unprimed T cells

Kawai

Matsumoto

Watanabe

et al. 1991

SUMMARYThe skin is a major target organ in human graft-versus-host disease (GVHD) after bone-marrow transplantation. GVHD can be induced in mice by i.v. injection of T cells into unirradiated semiallogeneic or lethally irradiated allogeneic recipients. However, in the murine systemic GVHD model, cutaneous lesions occur only in lethally irradiated recipients. Since lethal irradiation itself might induce the epidermal cell damage, several investigators have employed another murine model of cutaneous GVHD, in which cutaneous lesions were induced by intradermal injection of alloreactive T cell clones. Using this system, it has been reported that both MHC class I-and IIreactive T cell clones can induce cutaneous GVHD in non-irradiated or sublethally irradiated recipients. However, it has remained unknown whether or not freshly prepared T cells are able to induce cutaneous GVHD after local injection into non-irradiated recipients. We show that unprimed T cells can induce cutaneous GVHD after local injection into unirradiated MHC class II-or I + IIdisparate recipients. In contrast to alloreactive T cell clones, unprimed T cells could elicit only mild cutaneous lesions in MHC class I-disparate recipients. Since sublethal irradiation of MHC class Idisparate recipients did not result in the manifestation of cutaneous lesions after injection of unprimed T cells, host anti-donor responses by radiosensitive cells could not be responsible for this phenomenon. This experimental system provides a useful model for analysis of the regulation mechanisms in the induction of GVHD by unprimed T cells.