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The value of HL-A antigens as genetic markers and epidemiologic tools in various disease states is becoming increasingly apparent. The antigens of the HL-A system (the major histocompatibility locus in man) are found on most human cells, especially the leukocytes and cells of the epidermis and the dermis. Associations have recently been found for HL-A antigens in psoriasis. atopic dermatitis, systemic lupus ervthematosus, dermatitis herpetiformis, pemphigus vulgaris,. and malignant melanoma of the skin; in several other diseases, associations with HL-A antigens are also probably present. Two possible mechanisms of association of HL-A with various diseases are (1) a close linkage between a gene governing immunologic responsiveness to a disease and HL-A genes, or (2) antigenic (chemical) cross-reaction between HL-A antigens and the etiologic agent (e.g.. streptococci or viral capsular antigen) associated with the disease. [ABSTRACT FROM AUTHOR]

Mouse histocompatibility antigens were solubilized from lymphocyte membranes by limited papain degradation. Spleens from Balb/c mice (H-2d), enlarged by administration of lymphoma cells, were used for the membrane preparations. The solubilized protein components were purified by ion-exchange chromatography, gel filtration and discontinuous polyacrylamide-gel electrophoresis. A further characterization was achieved in a two-dimensional protein mapping system using disc-electrophoresis and isotachophoresis in the first and second dimension, respectively. The purification was monitored for alloantigens H-2.4(D) and H-3.21(K) (H-2D and H-2K represent two regions of the H-2 system). On Sephadex G-100 partially purified H-2-alloantigen chromatographed in a region of Mr = 35500. The pI of these substances showed a maximum at pH 5.5 and 5.3 for H-2.4 and at 5.2 for H-2.31. Free SH- and dithio-groups were determined with 5,5′-dithiobis(2-nitrobenzoic acid). 1.56 μmol SH/μmol alloantigenic material was found, but no SS-bond could be detected after alkaline cleavage. This suggests the absence of covalently linked protein subunits in papain-solubilized molecules bearing single private specificites. This was confirmed after reduction and alkylation in 4 M urea: 30-50% of the alloantigenic activity was retained and shown, in polyacrylamide-gel electrophoresis, to migrate in the original region of activity (RBPB 0.29 and 0.33 for H-2.4; about 0.33 for H-2.31, BPB = bromophenol blue). After reductive alkylation gel filtration resulted in a further purification of the alloantigenic material. Highly purified substances showed a diffuse staining pattern and a broad serological profile after electrophoresis. We assume this heterogenity to be a genuine property of H-2 antigens. Structural and genetic implications of these findings are discussed. [ABSTRACT FROM AUTHOR]

Cellular immune responsiveness, as measured by lymphocyte transformation in one-way mixed leucocyte cultures (MLC) and in phytohaemagglutinin (PHA) stimulated cultures was evaluated in forty patients with systemic lupus erythematosus (SLE) and in seventy-four normal controls. The effect produced by sera from these subjects on in vitro lymphocyte reactivity was tested on autologous cells and on homologous responding cells from a constant panel of ten healthy volunteers. The reactivity of lymphocytes from SLE patients to PHA and to a battery of allogeneic cells was significantly lower than that of normal controls. Sera from some SLE patients inhibited the MLC reactions, while in other cases a distinct stimulatory effect was found. It is suggested that virus-induced modifications of normal histocompatibility antigens cause the appearance of blocking antibody that might bind to the surface of T lymphocytes, impairing their function. [ABSTRACT FROM AUTHOR]

The exchange of tissues, most conveniently skin, between individuals has long afforded a means of evaluating their genetic identity or dissimilarity. The validity of the procedure depends upon the fact that in nearly all vertebrate species so far studied many different histocompatibility or H-loci, distributed on different chromosomes, determine isoantigenic specificities on the surfaces of virtually all nucleate cells of the body. The grafting of living tissue cells from a donor to a recipient of the same species results in rejection of the "homograft" unless the donor and recipient are members of the same highly inbred strain or they are identical twins.

The rejection of an organ or tissue transplant is immunological in nature and is the direct consequence of antigenic disparity between the transplant dotter and recipient. Cellular antigens, which differentiate individuals and cause the rejection of transplants, are defined as histocompatibility antigens. The immunologic properties of histocompatibiuty antigens are regulated by histocompatibility genes. The most comprehensive studies on the genetics of tissue transplantation were undertaken with the aid of highly inbred strains of laboratory mice. There evolved from a multitude of experiments performed in numerous laboratories a generally adopted rationale to account for the success or failure of tissue transplants.

Analyzes the biochemistry of antigens that influence histocompatibility. Properties of major histocompatibility loci; Application of an assay system to purify the substance; Location of the histocompatibility antigens according to tissue distribution, subcellular distribution and stabilization techniques.

Cells from thirty-three human lymphoid cell lines and sublines have been typed for HL-A antigens by a microcytotoxicity test. Similar patterns of HL-A antigens were found for the cell line cells and for the fresh lymphocytes of the donor of the line (eleven cases). However, certain typing sera gave positive reactions with the cell line cells which were not found with the fresh lymphocytes. No correlation was noted between the pattern of these 'extra' reactions and the HL-A typing of the cells. These same typing sera often gave positive reactions with blood lymphocytes cultured for several days in conventional media. These positive reactions were quantitatively more pronounced and sometimes qualitatively different if the cells had been stimulated. A range of normal sera failed to react with cell line cells suggesting that the HL-A typing sera giving 'extra' reactions are detecting antigens in some way related to a histocompatibility system. Absorption studies performed with two of the lines confirmed the HL-A typing by the direct cytotoxicity test. Two sera giving 'extra' reactions were also tested in the absorption experiments. The results indicated that antibodies other than those of the HL-A specificity designated for these sera were responsible for the 'extra' reactions. It is suggested that 'extra' reactions indicate a change in the apparent antigenic expression of lymphoid cells reflecting altered membrane characteristics as they adapt to a culture environment. [ABSTRACT FROM AUTHOR]

Intravenous donor antigen in the form of spleen cells can significantly potentiate the effects of ALS in prolonging the survival of skin allografts exchanged across both weak and strong histocompatibility barriers. This effect depends on the proper timing of antigen administration and can result in immunologic unresponsiveness of sufficient strength to permit acceptance of second set grafts. The skin allograft itself apparently plays a role in the establishment of this unresponsive state since ALS and antigen alone followed by delayed allografts at 21 days resulted in normal graft rejection times. [ABSTRACT FROM AUTHOR]

This study provides evidence in mice of three strain combinations, that the classical law of transplantation that one gene ⇄ one antigen is applicable. It fails to confirm the suggestion that genic interaction may operate between the histocompatibility loci. [ABSTRACT FROM AUTHOR]

Three instances of third party unresponsiveness in immunologically tolerant mice are reported. Tolerance was induced across the H-2 barrier. Runt disease was prevented by the use of (host × donor) F1 hybrid cells for tolerance induction. The rejection of third party grafts by F1 hybrids from crosses between the host strain and the tolerance inducing donor strain excluded antigenic overlap as a possible explanation for the phenomenon. Third party unresponsiveness was restricted to weak histocompatibility antigens. Skin grafts presenting the tolerant hosts with third party H-2 antigens were rejected with normal promptitude. CBA mice tolerant of A, and A mice tolerant of CBA retained C3H grafts significantly longer than (A × CBA) F1 hosts. It is suggested that this instance of third party unresponsiveness in reciprocally tolerant animals favours the interpretation that the phenomenon is due to incomplete specificity of induced immunological tolerance, rather than to an innate inability of the tolerant hosts to react against the relevant third party histocompatibility antigens. [ABSTRACT FROM AUTHOR]

By means of family studies the relation between leucocyte antigens and reactivity in mixed lymphocyte culture was investigated. The following conclusions could be drawn: (1) Mixed lymphocyte culture reactivity is completely dependent upon HL-A determined incompatibilities. (2) A difference for two alleles is in general accompanied by a stimulation about twice as high as in combinations with one allele in common. (3) The lymphocytes of three pairs of unrelated individuals, which showed serologically HL-A identical phenotypes, did react in the mixed lymphocyte culture. The implications of these results for histocompatibility testing are discussed. [ABSTRACT FROM AUTHOR]