PubMed Health⌕ Search

Biomedical subjects

J Forman

Publications and source records attributed to J Forman.

At least 109 records · Page 6Linked to original sources
PubMed1985

Recognition of an Igh-linked histocompatibility antigen, H-40, on B-cell tumors by cytotoxic T lymphocytes.

This article reviews our data on H-40, a histocompatibility antigen controlled by a locus linked to Igh structural genes but telomeric to Tsu. The antigen is detected by rejection of H-40+ tumor cells in vivo and by the activity of H-2 restricted anti-H-40 cytotoxic T lymphocytes in vitro. H-40 is expressed on lipopolysaccharide stimulated B cells and B cell tumors that express surface(s) IgM and not on sIgM- tumors or other neoplastic cells. Its expression on the sIgM,D+ BALB/c (Igha, H-40a) derived leukemia, BCL1, prevents its transplantability across the Ig heavy chain (and H-40) barrier into C.B-20 (Ighb, H-40b) mice; whereas, BALB/c tumors that do not express H-40 can be transplanted into this allotype-congenic recipient. Although irradiated C.B-20 animals are susceptible to the BCL1 tumor, adoptive transfer of a mixture of Lyt-2+ and Lyt-2- effector cells (anti-H-40) from C.B-20 animals that have previously rejected BCL1 protect such recipients. However, the same effector cells will not protect irradiated BALB/c or (BALB/c X C.B-20)F1 recipients from this tumor. Since normal BALB/c sIg+ cells express H-40, either the effector cells are diverted from interacting with and destroying the tumor, or recognition of H-40 on non-tumor cells elicits a suppressor mechanism.

Animals↗
PubMed1985

Identification of a unique tumor-specific antigen as a novel class I major histocompatibility molecule.

Cancers induced by physical or chemical carcinogens express tumor-specific antigens that are uniquely specific for any given tumor; therefore, there is a seemingly endless variety of these unique antigens. We have studied a UV-induced fibrosarcoma, designated 1591, to elucidate the obscure molecular nature and genetic origins of unique tumor-specific antigens. A monoclonal antibody raised against syngeneic 1591 tumor cells has unique tumor specificity. This tumor-specific monoclonal antibody precipitated from the tumor a 45-kDa molecule associated with a 12-kDa molecule having the pI of beta2-microglobulin. This and other evidence indicated that the 1591 tumor expresses a novel class I molecule. A 1591 variant selected for the absence of binding to the monoclonal antibody lacked the novel class I MHC molecule as well as reactivity with cytotoxic T lymphocytes specific for the 1591 tumor. Furthermore, tumor cells bearing the antigen are rejected while variants that have lost the antigen grow progressively. Fourteen of 14 host-selected progressor tumor variants lost reactivity with the monoclonal antibody and provided further evidence that this novel class I molecule is a transplantation antigen on the parental 1591 tumor required for immune rejection. The identification of a unique tumor-specific antigen as a novel class I major histocompatibility complex gene product allows us to search for the possible genetic mechanisms involved and to explore further the role such molecules play in tumor immunity and malignancy.

Animals↗
PubMed1985

Interaction of alpha 1 with alpha 2 region in class I MHC proteins contributes determinants recognized by antibodies and cytotoxic T cells.

The structure-function relationship of individual coding regions of class I mouse major histocompatibility complex proteins was studied by a combination of recombinant DNA, gene transfer techniques, and serologic and functional characterization. To examine the role of alpha 1 and alpha 2 regions in antibody and CTL recognition, the third exon of H-2Dd, Kd, and Ld transplantation antigen genes was replaced by the homologous coding region of the Qa-2-coded class I gene, Q6. We have chosen to carry out the exon shuffling experiments between these two different types of class I genes, because they are structurally similar and did not evolve to carry out identical functions. Therefore, it is less likely that the hybrid proteins will fortuitously recreate alpha 1-alpha 2 controlled functionally important determinants. The replacement of H-2 alpha 2 coding region with its Q6 counterpart had different effects on the expression of the three genes. The mutant H-2Dd gene transfected into L cells was expressed at high levels and retained several of the serologic determinants found on parental H-2Dd and Q6 domains. The serologic epitopes on the mutant H-2Kd-transfected cells were detectable at very low levels, whereas the product of the mutant H-2Ld gene could not be identified at all. Analysis of cells transfected with mutant H-2Dd gene with alloreactive and minor antigen(s)-restricted cytotoxic T cells indicated that the hybrid proteins lost the ability to be recognized by T cells. Our data suggest that cytotoxic T cells recognize conformational determinants composed of amino acids from alpha 1 and alpha 2 regions. Alternatively, it could be proposed that T cell recognition sites located in a single alpha 1 or alpha 2 protein region are susceptible to distortion upon alpha 1-alpha 2 interactions. Such susceptibility to conformational changes of the amino-terminal domain of transplantation antigens could be of functional importance for H-2-restricted antigen presentation.

Animals↗
PubMed1985

[Direct atriopulmonary anastomosis (modified Fontan) for single ventricle and its equivalents].

The modified Fontan procedure is being used in an increasing number of complex cyanotic cardiac lesions with pulmonary stenosis. Seven patients aged 11 to 24 years (average 17.5 years) underwent surgery by a technique derived from the Fontan procedure: direct atriopulmonary anastomosis without a tube or valve. The tricuspid valve when patent was closed with a patch. The diagnoses were: single ventricule (4 cases), Taussig-Bing anomaly (2 cases) and tricuspid atresia (1 case). All patients had associated pulmonary stenosis with low pulmonary vascular resistances. The great vessels were in L-malposition in 3 cases. The hospital mortality was nil. Transient atrial fibrillation was observed in 2 cases and was well tolerated clinically. The follow-up period ranges from 2 months to 4 years (average 2.3 years). All patients are acyanotic with no signs of right-sided failure and in sinus rhythm. Control cardiac catheterisation and angiography were performed in 6 cases and showed good function of the anastomosis and a mean atrial pressure of 14 mmHg. Direct atriopulmonary anastomosis offers a very acceptable surgical solution to certain forms of single ventricle or equivalent with low pulmonary pressures. The short and medium term results seem to be better than those of intraventricular repair.

Adolescent↗
PubMed1984

H-40, an antigen controlled by an Igh linked gene and recognized by cytotoxic T lymphocytes. I. Genetic analysis of H-40 and distribution of its product on B cell tumors.

C.B-20 ( Ighb ) mice challenged with BALB/c ( Igha ) spleen cells (or vice-versa) generate cytotoxic T lymphocytes (CTL) that recognize an antigen, H-40, controlled by an Igh-linked gene. The gene maps to the Igh-C region end of the Igh complex, telomeric to Tsu in the region of Pre-1. At least three alleles, a, b, and c, can be defined. Using a cold target competition assay, no polymorphism of the a allele was detected. Both surface Igh-5a positive and negative spleen cells from (C.B-20 X BALB/c)F1 animals express the a allele of the antigen, indicating that this gene is not allelically excluded. Recognition of the target antigen by CTL is restricted by the D-end of H-2d. The tissue distribution of H-40 was explored using both bulk-cultured and cloned CTL. The antigen is expressed on surface immunoglobulin positive (sIg+) cells and correlates with the expression of sIgM. This was determined by analysis of several B lymphomas as well as of other tumors that varied in their extent of expression of sIg. Four subclones of BCL1 were analyzed. Two of the subclones are sIg+ and express H-40, while two other subclones are sIg- and H-40-. Thus, these data define an Igh-linked gene, separate from immunoglobulin structural loci, that controls an antigen expressed on sIg+ cells. Possible mechanisms to account for this finding are discussed.

Alleles↗
PubMed1984

Cytotoxic T lymphocytes recognize determinants on the BALB/c-H-2Ld molecule controlled by alpha 1 and alpha 2 but not alpha 3 external domains.

We have shown that cytotoxic T lymphocytes (CTL) raised in H-2d mice use H-2Ld but not H-2Dd or H-2Kd antigens as restricting elements in lymphocytic choriomeningitis virus (LCMV) and vesicular stomatis virus (VSV) infections. To localize the regions of H-2Ld protein recognized by CTL, we constructed a recombinant H-2Ld/Dd gene encoding a hybrid antigen with alpha 1 and alpha 2 external domains of H-2Ld and alpha 3, transmembrane and cytoplasmic domains of H-2Dd. The recombinant gene was transfected into mouse cells and the hybrid molecules were characterized serologically, biochemically and functionally. In all assays, H-2Ld/Dd molecules were recognized by LCMV-and VSV-specific H-2Ld-restricted CTL in a manner similar to that of wild-type H-2Ld antigens. Analogous results were obtained with alloreactive CTL. Hybrid antigens containing the alpha 3 domain of H-2Ld fused to alpha 1 and alpha 2 domains of a Qa-2,3 region-encoded antigen were not used as restricting elements by LCMV-specific CTL. These results suggest that H-2Ld-restricted CTL directed against LCMV and VSV recognize determinants controlled by the alpha 1 and/or alpha 2 domains of the H-2Ld molecule.

Animals↗
PubMed1984

T cells, the MHC, and function.

The model presented relates the class of MHC molecule recognized with the activity of T lymphocytes. This occurs by postulating that the function of MHC molecules is to present determinants to differentiation directing (D) receptors on T lymphocytes. These D receptors are distributed nonclonally and interact with nonpolymorphic determinants on MHC molecules which are normally inaccessible. The result of this interaction is to allow for the expression of a functional phenotype for the T cell providing that helper signals are present. In the case of alloreactive CTL that recognize class II or Th that recognize class I molecules we postulate that these T cells require the presence of class I or class II molecules, respectively, on the target cell. Recognition of antigen in the absence of helper signals leads to tolerance of both Th.P and CTL.P. Since helper signals are required for the activation of CTL.P, a lack of specific Th, determined by class II alleles, will prevent development of a proportion of the CTL repertoire.

Animals↗
PubMed1984

H-40, an antigen controlled by an Igh-linked gene and recognized by cytotoxic T lymphocytes. II. Recognition of H-40 as a tumor antigen in leukemic animals.

C.B-20 (Ighb) but not (C.B-20 X BALB/c)F1 mice reject BCL1, a sIg+ tumor that spontaneously arose in an Igh congenic BALB/c (Igha) mouse. C.B-20 immune T cells from mice immunized with either BCL1 or BALB/c splenocytes adoptively transfer tumor protection to sublethally irradiated C.B-20 but not BALB/c or (BALB/c X C.B-20)F1 mice. These data suggest that BALB/c and BCL1 share an antigen, which if present in the host prevents the immune cells from eradicating the tumor. The antigen is controlled by H-40, a gene that maps to the C end of the Igh complex, telomeric to Tsu and in the region of Pre-1. The ability of H-40 to act as a tumor antigen for other BALB/c tumors inoculated into C.B-20 hosts was investigated. H-40 did not elicit rejection of P1798 (T lymphoma), Meth A (fibrosarcoma), or MOPC-315 (alpha, lambda myeloma) tumor cells. C.B-20 mice that previously rejected BCL1, however, showed partial resistance to a low challenge dose of the MOPC-104E (mu, lambda myeloma) tumor. These data suggest that H-40 has a differential degree of expression on BALB/c tumor cells. The ability of the adoptively transferred cells to confer protection against BCL1 is abrogated by pretreatment of the cells with anti-Lyt-1 or anti-Lyt-2 antibodies. However, an admixture of anti-Lyt-1- and anti-Lyt-2-treated cells provided protection. These data, together with the results detected by cytotoxic T lymphocyte (CTL) activity in vitro, indicate that H-40 can serve as a target antigen for tumor rejection by CTL in allogeneic hosts. The implications of the results for allogeneic bone marrow transplantation into leukemic individuals who benefit from a graft vs leukemia effect are discussed.

Animals↗
PubMed1983

Use of DNA-mediated gene transfer to analyze the role of H-2Ld in controlling the specificity of anti-vesicular stomatitis virus cytotoxic T cells.

Mouse thymidine kinase (tk-) C3H L (H-2k) cells transformed by the technique of DNA-mediated gene transfer with the herpes simplex virus tk gene together with the BALB/c H-2Ld gene express H-2Ld molecules indistinguishable from their counterparts on spleen cells. An established cloned cell line (8-5) was used to assess the function of the H-2Ld antigen in determining the specificity of alloreactive as well as anti-vesicular stomatitis virus (VSV) cytotoxic T cells (CTL). Both anti-H-2d and anti-H-2Ld CTL displayed a cytotoxic effect against 8-5 cells but not a control cell line transformed with the tk gene only (tk+ cells). Further evidence that 8-5 cells express H-2Ld was provided by the finding that monoclonal anti-H-2Ld but not H-2Dd antibodies blocked target cell lysis by the effector cells. Both BALB/c (H-2d) and DBA/2 (H-2d) animals generated anti-VSV CTL that lysed infected 8-5 but not tk+ cells. To further establish that H-2Ld controlled the specificity of the effector cells, a monoclonal antibody directed against H-2Ld was shown to inhibit lysis of infected 8-5 target cells. To determine whether other H-2d-encoded gene products could serve as restricting antigens for anti-VSV CTL in BALB/c animals, unlabeled VSV infected 8-5 cells were tested for their ability to block lysis of 51chromium-labeled P815 (H-2d)-infected target cells. The 8-5-VSV inhibitor cells inhibited lysis to a slightly lesser extent than unlabeled P815-VSV cells, indicating that H-2Ld plays a major if not exclusive role in restricting anti-VSV CTL in H-2d animals.

Animals↗
PubMed1983

Expression and function of transplantation antigens with altered or deleted cytoplasmic domains.

Two mutants of the class I gene encoding the H-2Ld transplantation antigen have been constructed. In one mutant the cytoplasmic domain of the class I molecule has been altered by deletion of 24 of the 31 C-terminal residues, and in the second the C-terminal 25 residues of the cytoplasmic domain have been replaced with a unique sequence of 19 amino acids. These mutant class I genes have been transferred into mouse L cells by DNA-mediated gene transfer. Both mutant genes are expressed at normal levels on the cell surface, and they have charge properties and sizes consistent with the introduced alterations. These mutant Ld molecules can serve as target antigens for allogeneic cytotoxic T cells and as restricting elements for virus-specific cytotoxic T cells. These results show that the 24 residues replaced or deleted from the carboxy terminus of the class I molecule are not required for its transport to or integration in the plasma membrane, nor for its function as a target antigen or a restricting element during T-cell-mediated cytotoxicity.

Amino Acid Sequence↗
PubMed1983

Non-invasive quantification of aortic regurgitation by Doppler echocardiography.

This study was undertaken to assess the contribution of Doppler echocardiography to the quantification of aortic valve regurgitation. Ultrasound examination was performed by recording aortic arch blood flow from the suprasternal notch. A non-invasive index of valve regurgitation was obtained by calculating the ratio between the maximal amplitude of forward flow during systole and the amplitude of retrograde flow during diastole measured at the onset of the R wave of the electrocardiogram. This index was compared with semiquantitative data derived from supravalvular aortography in 93 patients. In pure aortic regurgitation (67 patients) the results showed a high correlation coefficient between Doppler and angiographic estimates. In cases of associated aortic valve stenosis there were problems in the accurate estimation of systolic blood flow which led to global overestimation in general of the degree of regurgitation and considerable lack of precision in individual patients. But in general Doppler echocardiography appeared to be a successful technique to quantify pure aortic regurgitation.

Adolescent↗
PubMed1983

Quantitative assessment of tricuspid regurgitation using pulsed Doppler echocardiography.

Tricuspid valve regurgitation was assessed quantitatively by measuring blood flow velocity in the vena cava using a pulsed Doppler velocimeter. A non-invasive index of regurgitation was obtained by calculating the ratio between the maximum amplitudes of the systolic and diastolic components of the velocity curves. The index was compared with the angiographic grading of regurgitation in 70 patients after right heart catheterisation; the results were closely correlated. Using the Doppler index the differences between the groups defined according to their angiographic grade were significant. Thus measurement of blood flow velocity in the vena cava appears to quantify accurately the severity of tricuspid regurgitation.

Adolescent↗
PubMed1983

Allogeneic and associative recognition determinants of H-2 molecules.

Data presented here describe recent attempts to understand the structural basis for H-2 function. Inbred strains differing only by point mutation in different regions of H-2Kb have proven valuable in the analysis of H-2 domain function. Evidence for the interaction between the N and C1 domains in forming allorecognition determinants and antigen interaction sites is shown. The functional role of C2 is not yet known, since no mutations have been found there, but DNA-mediated gene transfer and exon shuffling techniques should prove invaluable in addressing this issue. Ir gene-type functions of class I molecules were demonstrated. The inability of low responder mutant strains to cross-react with H-2Kb-restricted CTL suggests that these phenomena reflect the failure of virus antigen to interact with low responder H-2Kbm molecules. Thus, the mutant strains provide a valuable system for investigating class I Ir genes.

Animals↗