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Results for “Histocompatibility”

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At least 19 recordsLinked to original sources

PubMed1990

Ia restriction specificity of KLH-specific T cells from allogeneic bone marrow chimeras is influenced by histocompatibility at the H-2 and minor histocompatibility loci.

Ia restriction specificity involved in T cell proliferative responses to keyhole limpet hemocyanin (KLH) has been analyzed using a variety of allogeneic bone marrow chimeras. The chimeric mice were prepared by reconstituting irradiated AKR, SJL, B10.BR and B10.A(4R) mice with bone marrow cells from B10 mice. When such chimeric mice had first been primed with KLH in complete Freund's adjuvant (CFA), T cells from H-2 incompatible fully allogeneic chimeras showed significantly higher responses to KLH in the presence of antigen-presenting cells (APC) of donor strain (B10) than APC of recipient strain. However, in H-2 subregion compatible chimeras, [B10----B10.A(4R)], which were matched at the H-2D locus and at minor histocompatible loci, the T cells could mount vigorous responses to KLH with antigen-presenting cells (APC) of either donor or recipient type. The same results were obtained as well with chimeras that had been thymectomized after full reconstitution of lymphoid tissues by donor-derived cells. A considerable proportion of KLH-specific T cell hybridomas established from [B10----B10.A(4R)] chimeras exhibited both I-Ab and I-Ak restriction specificities. The present findings indicate that the bias to donor Ia type of antigen specific T cells is determined by donor-derived APC present in the extrathymic environment but that cross-reactivity to the recipient Ia is influenced to some degree by histocompatibility between donor and recipient mice, even though the histocompatible H-2D locus and minor histocompatibility loci seem not to be directly involved in the I-A restricted responses studied herein.

Animals↗

PubMed1987

Aberrant expression of class II major histocompatibility complex molecules by B cells and hyperexpression of class I major histocompatibility complex molecules by insulin containing islets in type 1 (insulin-dependent) diabetes mellitus.

Twenty-three patients with recent onset Type 1 (insulin-dependent) diabetes in whom residual insulin secreting B cells were present and 12 patients with disease of more prolonged duration (maximum 9 years), 8 of whom had residual B cells, were studied. Aberrant expression of Class II major histocompatibility complex molecules was demonstrated immunohistochemically on insulin secreting B cells in 21 out of 23 patients with recent onset disease and 6 of the patients with more prolonged disease. No such expression was seen on glucagon secreting A cells or somatostatin secreting D cells. Islets where there was marked hyperexpression of Class I major histocompatibility complex molecules on islet endocrine cells were seen in all cases in which residual B cells were present. Ninety-two per cent of insulin containing islets but only 1% of insulin deficient islets exhibited this phenomenon (p less than 0.001, Chi-squared test). There was evidence to suggest that both these abnormalities of major histocompatibility complex expression preceded insulitis within a given islet. They also appeared to be unique to Type 1 diabetes, being absent in pancreases of patients with Type 2 (non-insulin-dependent) diabetes, chronic pancreatitis, cystic fibrosis, graft-versus-host disease and Coxsackie B viral pancreatitis. The development of autoimmunity to B cells in Type 1 diabetes may be a "multistep" process in which abnormalities of major histocompatibility complex expression on islet endocrine cells are crucial events.

Adolescent↗

PubMed1980

Genetic definition of a further gene region and identification of at least three different histocompatibility genes in the rat major histocompatibility system.

Two new recombinant haplotypes of the rat major histocompatibility system, RT1, have been detected in [LEW.1A (RT1a) x LEW.1W (RT1U)] x LEW.1N(RT1n) segregating hybrids. Recombinant r3 carries the RT1.A region (determining classical transplantation antigens) and the RT1.B region (determining strong mixed lymphocyte reactivity and genetic control of antipolypeptide immune responsiveness) of the RT1a parent, bur rejects RT1a skin grafts. Recombinant r4 carries the A and B regions of the RT1u parent, but rejects RT1u skin grafts. The two histocompatibility genes detected are allelic to each other. The relevant locus, designated as H-C, maps to the B-region side of the RT1 system and appears to mark a third RT1 gene region, RT1.C. Availability of haplotypes r3 and r4 allowed the definition of a histocompatibility locus in the B region, H-B. The products of H-C, H-B and of the previously described H-A gene vary in antigenic strength.

Animals↗

PubMed1980

Creation and properties of histocompatibility antigen-cell conjugates. II. Antibody tolerance after treatment with donor histocompatibility antigen chemically coupled to recipient spleen cells.

Histocompatibility (HC) antigens from Lewis (RT-11) and ACI (RT-1a) rats were solubilized and their tolerogenic potential alone or when conjugated to cellular carriers was investigated. The tolerogenic carrier potential of whole cells, crude membranes, and deoxycholate (DOC)-solubilized membranes was first determined by conjugating trinitrophenyl (TNP) groups to them and measuring their ability to prevent an anti-TNP plaque-forming cell response in rats after immunogenic challenge. Since whole lymphoid cells proved to be most effective in this system, DOC-solubilized allogeneic histocompatibility antigens were coupled to syngeneic lymphocytes, using carbodiimide cross-linking. Animals pretreated with this conjugate produced no alloantibody upon challenge with allogeneic cells. These results suggest that tolerance to allogeneic histocompatibility antigen can be produced by association of alloantigens on a tolerogenic self-carrier.

Animals↗

PubMed1980

Major histocompatibility complex-restricted and unrestricted T helper cells recognizing minor histocompatibility antigens of B cell surfaces.

The present experiments analyze the functional properties of helper T cells specific for "minor" histocompatibility antigens. T cells from C3H/HeJ mice, primed in vivo and highly enriched in vitro for reactivity to membrane antigens of C3H/Tif B cells, specifically proliferate, and provide polyclonal help to splenic B cells from strains carving a variety of different H-2 haplotypes on C3H or BALB backgrounds, while failing to respond to cells carrying the same H-2 haplotypes on C57BL or A backgrounds. Since it has been previously demonstrated (A.A. Augustin and A. Coutinho, J. Exp. Med. 1980. 151: 587) and B cell activation in this system strictly requires direct, specific recognition of B cell surface antigens by helper cells and does not result from the production of soluble "mitogenic" or "nonspecific helper factors", it is concluded that this phenomenon represents specific, major histocompatibility complex (MHC)-unrestricted T cell help. In addition, it has now been found that expression of helper activity requires viability of the helper cells and is partially radiation-sensitive. Lack of MHC restriction is not a general property of specific helper cells which directly recognize B cell "minor" antigens, since BALB.C3H anti-C3H/Tif T cells appear to be restricted by H-2 in their polyclonal helper activity. The helper activity mediated by specific anti-"minor", H-2 restricted helper cells could not be inhibited by anti-VH antibodies, and the inhibition obtained with anti-Ia antibodies appeared to operate at the level of B cell induction, rather than at the level of helper cell activation.

Animals↗

PubMed1971

Histocompatibility studies in a closely bred colony of dogs. II. Influence of the DL-A system of canine histocompatibility upon the survival of cardiac allografts.

The DL-A system of histocompatibility plays an important role in conditioning the survival of cardiac allografts in the unmodified canine host. The mean survival time of six cardiac allografts performed in DL-A-compatible littermate dogs obtained from a closely bred colony of beagles was 53.2 days, while the MST of transplants performed in seven DL-A-incompatible animals was 7.3 days. The MST of cardiac allografts performed in nine DL-A-compatible nonlittermate beagles was 26.3 days, as compared with 6.3 days in six DL-A-incompatible nonlittermate transplants. The results did not appear to be affected by Swisher erythrocyte-group incompatibilities. The MST of 28 cardiac allografts performed in randomly selected mongrel dogs was 10.0 days. Incompatibilities for DL-A antigens e, f, g, l, and m may constitute major barriers to transplantation, but antigens b, c, d, and k appeared to act as weak histocompatibility antigens. Under controlled conditions of donor-recipient DL-A compatibility, cardiac allografts may be less immunogenic than renal transplants. Heart transplants performed across major donor-recipient DL-A incompatibilities appeared, however, to be more vulnerable to the events of allograft rejection than renal allografts performed under similar conditions. The selection of optimally compatible donor-recipient combinations for organ transplantation may be aided materially by genetic studies of the transmission of DL-A antigens to the animals under consideration.

Animals↗

PubMed1975

The major histocompatibility complex determines susceptibility to cytotoxic T cells directed against minor histocompatibility antigens.

Cytotoxic cells were generated by immunizing one strain of mouse with cells from an allogeneic strain which carries the same H-2 region. The effector cells assayed in a 4 h 51Cr release assay were shown to be T cells and indistinguishable, except in specificity, from cytotoxic T cells directed at H-2 alloantigens. Although the genetic differences between responder and stimulator cells responsible for the immunization did not code in H-2, the H-2 complex did restrict susceptibility of target cells. For example, BALB.B cytotoxic cells (H-2b) immunized against and capable of lysing C57BL/6 cells (H-2b) would not lyse B6.C/H-2d target cells. C57BL/6 and B6.C/H-2d are congenic and differ in the H-2 region. Two hypotheses are considered to explain the H-2 restriction of susceptibility to cytotoxic T cells generated by an H-2 identical alloimmunization. (a) The dual (self) recognition hypothesis states that the cytotoxic cell has two recognition units, one for H-2-coded structures and another clonally restricted receptor for the minor alloantigen. (b) The interaction antigen hypothesis states that all the surface alloantigenic determinants recognized by cytotoxic T cells are the result of interaction between H-2- and non-H-2-coded gene products. Two lines of evidence, one with F1 effector cells and the other a cold target competition experiment, are presented which argue strongly in favor of the interaction antigen hypothesis. The regions of H-2 required to be histocompatible were mapped to the D region and to the left of IC, probably the K region. These results, and recent work on the response to virus-infected and TNP-modified syngeneic cells, suggest that cytotoxic cells are restricted in specificity to preferentially recognizing alterations in structures that are coded in the major histocompatibility complex.

Animals↗

PubMed1991

Cell-cell adhesion mediated by CD8 and human histocompatibility leukocyte antigen G, a nonclassical major histocompatibility complex class 1 molecule on cytotrophoblasts.

The lymphocyte differentiation marker CD8 acts as a coreceptor with the T cell receptor (TCR) during recognition of peptide presented by major histocompatibility complex (MHC) class I molecules. The functions of CD8 in the TCR complex are thought to be signaling through the association of CD8 with the protein tyrosine kinase p56lck and adhesion to MHC class I through the alpha 3 domain. While the ability of the CD8 alpha/alpha homodimer to bind to classical MHC class I molecules has been shown, it is unclear whether CD8 can also bind nonclassical molecules. Of particular interest is human histocompatibility leukocyte antigen (HLA)-G which is expressed on placental cytotrophoblast cells. These cells do not express HLA-A, -B and -C molecules. In this report, we demonstrate that CD8 can bind to HLA-G. It is possible, therefore, that a cell bearing CD8 may interact with HLA-G-expressing cells.

Antigens, CD↗

PubMed1979

Tolerance to non-H-2 histocompatibility antigens. Transplantation tolerance to the H-4 and H-7 histocompatibility antigens.

There have been several reports of observations which suggest that transplantation tolerance may be a result of positive immunoregulation rather than simply unresponsiveness attributable to a lack of competent effector cells. In particular, several investigators have reported that tolerance of the H-Y and H-1 histocompatibility antigens is mediated by a population of thymus-derived lymphocytes. In a companion report, we have presented evidence that supports the existence of a suppressor cell to the H-Y antigen. Furthermore, we have observed that female mice rendered tolerant of the H-Y antigens by neonatal exposure to male lymphoid cells or by multiparity accept male skin grafts indefinitely, but inactivate male peritoneal exudate cells (PEC) in a second-set fashion. This observation has led us to investigate whether tolerance of other non-H-2 antigens is controlled by a similar mechanism. Using mice congenic with C57BL/10 at the H-4 and H-7 loci, we have shown that mice rendered tolerant of the H-7a and H-4b antigens by neonatal exposure to histoincompatibe lymphoid cells are incapable of rejecting either skin or peritoneal cell allografts, suggesting that identical histocompatibility antigens are present on skin and peritoneal cells. Tolerance induced in neonatal mice to the H-4b and H-7a antigens could not be adoptively transferred to syngeneic recipients. These results suggest that tolerance involving the H-4 and H-7 antigens is most likely because of a clonal inactivation of alloantigen-reactive cells as a consequence of neonatal exposure to antigen.

Animals↗

PubMed1979

Major histocompatibility complex products restrict the adherence of cytolytic T lymphocytes to minor histocompatibility antigens or to trinitrophenyl determinants on schistosomula of Schistosoma mansoni.

We have previously shown that schistosomula passaged through mice acquire histocompatibility (H) antigens that can be recognized either by alloantibody or by alloreactive cytolytic T lymphocytes (CTL). The latter specifically adhere to but fail to damage the parasite. In this paper we describe the use of trinitrophenyl (TNP)-labeled schistosomula to show that the adherence of CTL with specificity for TNP-modified syngeneic cells is restricted by the major histocompatibility complex (MHC) in a fashion similar to that seen in the lysis of TNP-labeled tumor targets. Thus, these CTL adhere only to schistosomula that have both the appropriate H antigens and TNP determinants on their surface, and not to schistosomula bearing either of these antigens by themselves. We note a significant degree of adherence to schistosomula bearing TNP determinants and H antigens allogeneic to the CTL. Anti-minor H antigen CTL are also restricted by the MHC in their adherence; thus, they only adhere to schistosomula that carry both the major and minor H antigens of the stimulator cells. These antigens can be acquired either by a single passage in vivo of schistosomula through congenic strains that possess both the relevant antigens or by sequential passage through two different strains, each contributing one of the antigens in question.

Animals↗

PubMed1978

Major histocompatibility complex and non-major histocompatibility complex antigens on mouse ectoplacental cone and placental trophoblastic cells.

The expression of major histocompatibility complex and non-major histocompatibility complex antigens on mouse trophoblast cultured from two defined stages of development was investigated by the sensitive in vitro mixed haemadsorption assay. Outgrowths obtained 3 to 5 days after explanation of 7 1/2-day ectoplacental cones contained a mixed population of cells. Those with a giant cell morphology showed no haemadsorption with congenic H-2 antisera and were reactive with non H-2 antiserum only in the CBA strain. Other, smaller cells were reactive for both H-2 and non-H-2 in all strains examined except for C57BL, where the cells were nonreactive for H-2. Monolayer cultures of 13 to 14-day placental suspensions tested 24 hr after preparation were strongly reactive for both H-2 and non-H-2. The identity and alloantigenic status of the cells are discussed in relation to their function in maternal-foetal immunological interactions.

Animals↗

PubMed1980

Creation and properties of histocompatibility antigen-cell conjugates. I. Preparation and immunological properties of rat histocompatibility antigens.

A necessary step in the induction of unresponsiveness to transplantation antigens is the preparation and presentation of tissue antigens in a suitable form. A method is presented for obtaining rat histocompatibility antigen in a soluble, "heptenic" form suitable for coupling to a tolerogencie carrier. Lewis and ACI spleen cell membranes are solubilized with deoxycholate and purified by Lens culinaris affinity chromatography. The ultracentrifuged, solubilized preparation of rat histocompatibility (HC) antigen is unable to initiate immunity, but is able to react specifically with the product of an already established immune response. The HC antigen preparation is neither immunogenic nor tolerogenic alone. However, an antibody response to allogeneic cells can be prevented when these rat HC preparations are chemically coupled to tolerogenic carrier as described in the accompanying paper.

Animals↗

PubMed1990

The class II major histocompatibility complex antigen deficiency syndrome: consequences of absent class II major histocompatibility antigens for lymphocyte differentiation and function.

The class II major histocompatibility complex antigen deficiency syndrome is a rare immunodeficiency disease associated with defective expression of the class II antigens encoded for by the major histocompatibility complex. Clinically, this syndrome is manifest as a combined immunodeficiency presenting early in life, and affected individuals are susceptible to a variety of severe and/or opportunistic infections. Chronic, severe diarrhea and malabsorption are also characteristically found, and death is common within the first few years of life. Although the precise molecular lesions responsible for the failure of membrane antigen expression in this syndrome have not yet been identified, the pathogenetic mechanisms involve regulatory defects in the transcription of structural genes encoding for class II antigens. The absence of class II MHC antigens results in profound abnormalities in lymphocyte function and differentiation. Of central importance is the defective MHC-restricted interactions between CD4+ "helper" T lymphocytes and the various types of antigen-presenting cells found in the skin and elsewhere. The absence of class II MHC antigens also appears to alter the ability of affected B cells to be activated by a variety of membrane-mediated stimuli, and it profoundly disrupts both the intrathymic development and post-thymic differentiation of immunoregulatory T cells. This "experiment of nature" thus demonstrates the critical role of class II MHC antigens in the proper development and function of the immune system.

Animals↗

PubMed1986

Immunodominance in the T cell response to multiple non-H-2 histocompatibility antigens. III. Single histocompatibility antigens dominate the male antigen.

Immunization of mice with multiple non-H-2 histocompatibility antigens results in the generation of cytolytic T lymphocytes that are specific for a limited number of immunodominant antigens. The experiments presented in this communication were designed to reveal immunodominance in pairwise combinations of autosomal and sex-linked non-H-2 histocompatibility (H) antigens. Priming and boosting responders with the male antigen, H-Y, paired with the H-4.2, H-7.1, or H-3.1 antigens, resulted in the generation of cytolytic T cells specific for the autosomal H antigens but not the H-Y antigen. Furthermore, co-immunization and boosting of C57BL/6 female responder spleen cells with BALB.B male cells resulted in the generation of cytolytic T cells specific for the BALB.B immunodominant antigens but not H-Y. No dominance was observed in H-4-plus H-7-incompatible combinations. Co-immunization of three different H-3 congenic strains with H-3.1 plus H-Y demonstrated that an efficient anti-H-3.1 T cell response is required for observing H-3.1 immunodominance over H-Y. Co-expression of H-3.1 and H-Y on the same priming and boosting cells was required for immunodominance. In fact, immunization with H-3.1 and H-Y presented on different cells resulted in normal generation of H-Y-specific cytolytic T cells, but no generation of H-3.1-specific cytolytic T cells resulted unless H-Y-specific cells were stimulated in the mixed lymphocyte cultures. These observations suggest that in vitro T cell responses to paired, non-H-2 H antigens may be independent, competitive, or synergistic, depending on the identity of the antigens and the priming and boosting conditions.

Animals↗

PubMed1986

The major histocompatibility complex class I heavy chain as a structural subunit of the human cell membrane insulin receptor: implications for the range of biological functions of histocompatibility antigens.

Monoclonal antibodies against some of the monomorphic determinants of major histocompatibility complex (MHC) class I molecules reduce insulin binding and precipitate 125I-labeled insulin receptor preparations. A monoclonal antibody with specificity for the insulin binding site on the cell membrane insulin receptor of human cells was used to precipitate insulin receptors from human cell lines and resulted in distinct bands of Mr approximately 130,000, 90,000, and 45,000. The Mr 45,000 molecules thus precipitated were subjected to NaDodSO4/PAGE, eluted from the gels, and found to react with monoclonal antibodies against monomorphic and a polymorphic MHC class I determinant known to be expressed on the cell line used as receptor source. Moreover, a murine thymoma line (RI) with MHC class I expression bound significant amounts of insulin, whereas a MHC class I-negative variant had low insulin binding capacity. Reduction in the density on human cells of the MHC class I heavy chain was obtained by capping with antibodies to beta 2-microglobulin or to the MHC class I heavy chain and resulted in decreased insulin binding, whereas down-regulation of insulin receptors induced increased density of MHC class I molecules. It is concluded that the MHC class I heavy chain and the tetrameric insulin receptor are structurally associated in the cell membrane and suggested that this association may occur by displacement of beta 2-microglobulin by the insulin receptor.

Antibodies, Monoclonal↗

PubMed1995

Presensitization by skin grafting from major histocompatibility complex class I or major histocompatibility complex class II deficient mice identifies class I antigens as inducers of allosensitization.

Livers but not hearts are accepted spontaneously without immunosuppression when transplanted from B10 (KbAbEbDb) to C3H (KkAkEkDk) mice. Both organs however, undergo accelerated rejection in C3H recipients presensitized with B10 skin grafts. In this study, we have investigated further the role of functional cell-surface major histocompatibility complex (MHC class I or class II molecules in allosensitization. Skin from transgenic MHC class I (b2mmlUncbcr; AbEb) or class II (C2DTM, KbDb) gene 'knockout' mice was grafted onto naive recipients 2-3 weeks prior to whole organ transplantation. When C3H hosts were presensitized with skin from C2DTM (class II deficient) mice, they promptly rejected (within 4 days) subsequently transplanted B10 liver or heart allografts. In contrast, presensitization with skin from b2m (beta 2-m mutant; class I deficient) mice did not significantly affect the survival of either organ graft. Maximal sensitization was established by day 14 after skin grafting and persisted for at least 12 weeks. Splenocytes obtained from C3H mice sensitized with skin from B10, B6 (KbAbEbDb), or C2DTM but not from b2m mice exhibited an H-2b-specific cytolytic response when tested in cell-mediated lymphocytotoxicity assays. Sera from C3H mice sensitized with B10 or b2m skin contained high titres of cytotoxic activity specifically against H-2b class I. Taken together, these observations suggest that in the strain combination studied, MHC class I rather than class II molecules play an important role in allosensitization. The results indicate the potential importance of avoiding transplantation of organs into recipients of secondary grafts from donors that share human leucocyte antigen (HLA) class I antigens with the first donor.

Animals↗

PubMed1991

Evolution of the major histocompatibility complex: molecular cloning of major histocompatibility complex class I from the amphibian Xenopus.

Class I major histocompatibility complex (MHC) cDNA clones have been isolated from an expression library derived from mRNA of an MHC homozygous Xenopus laevis. The nucleotide and predicted amino acid sequences show definite similarity to MHC class I molecules of higher vertebrates. The immunoglobulin-like alpha-3 domain is more similar to the immunoglobulin-like domains of mammalian class II beta chains than to those of mammalian class I molecules, and a tree based on nucleotide sequences of representative MHC genes is presented.

Amino Acid Sequence↗

PubMed1971

Histocompatibility studies in a closely bred colony of dogs. 3. Genetic definition of the DL-A system of canine histocompatibility, with particular reference to the comparative immunogenicity of the major transplantable organs.

The segregation of the canine DL-A leukocyte group antigen(s) b, c, d, e, f, g, h, k, l, and m has been traced in 141 consecutive matings in the Cooperstown Colony of beagles. All of the leukocyte antigen(s) were regularly transmitted en bloc from parent to offspring, with no instance of independent segregation. A total of 23 haplotypes, including six different DL-A antigen patterns (gl, bkhfm, bkcd, e, be, fgl) was observed. 31 different DL-A phenotypes were observed in a population of 100 mongrel dogs. A number of statistically significant positive and negative associations between individual DL-A antigenic components occurred in this population. The results support the concept of the DL-A system as a complex immunogenetic system governed by a single region (or locus) of an autosomal pair of chromosomes. Studies of skin, kidney, heart, and liver allografts in the Cooperstown Colony indicated that the longest allograft survivals occur under genetically and serologically defined conditions of donor-recipient DL-A compatibility. Skin and renal allografts generally behaved in parallel fashion, while cardiac allografts survived for longer periods of time (MST = 47.1 days) than kidneys (MST = 28.1 days) or skin (MST = 25.1 days) under conditions of DL-A identity. Heart transplants were rejected at a more rapid rate than kidney, however, in DL-A-incompatible donor-recipient combinations. Liver transplants were accorded the longest survival time (MST = 76.2 days) under conditions of DL-A identity, but were rejected at a rapid rate (MST = 5 days) in DL-A-incompatible nonlittermate donor-recipient pairs. The results provide further evidence that the DL-A system is the principal system of histocompatibility in the canine species. The differences in survival of different organs under similar conditions of donor-recipient DL-A compatibility suggest, however, the existence of a number of unknown variables which may also be capable of significantly affecting allograft behavior.

Animals↗