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T J Gorzynski

Publications and source records attributed to T J Gorzynski.

16 recordsLinked to original sources

The Hb-2d cross-reactive idiotype. A common idiotype expressed by monoclonal and polyclonal antibodies to human haemoglobin.

Hb-2d is a monoclonal antibody of B10.D2 origin that is specific for the beta chain of human adult haemoglobin (HuHb-beta). Polyclonal anti-idiotypic sera to Hb-2d were produced in B10.D2, SJL/J and BALB/c mice. Using anti-idiotypic sera from SJL/J it was observed that Hb-2d expresses a cross-reactive idiotype (CRI) also found on both polyclonal and monoclonal antibodies to HuHb. Polyclonal antisera against HuHb-beta from H-2 congenic mice on the C57BL/10 (B10) background contained antibodies expressing the Hb-2d CRI; these antisera, however, contained little if any antibody to the antigenic determinant on HuHb-beta recognized by Hb-2d. Polyclonal antisera to HuHb-beta from the strains A.CA, A.SW, C3H.OL, BALB/cByJ, DBA/2 and SJL/J contained lower, but nevertheless detectable, amounts of antibody expressing the Hb-2d CRI. Unlike B10-H-2 congenic mice, antisera from the strains A.CA, A.SW and BALB/c bound to the same or a closely associated determinant as that recognized by Hb-2d. Two anti-HuHb monoclonal antibodies, Hb-48a and Hb-53a, both derived from B10-H-2 congenic mice, were shown to possess at least part of the Hb-2d idiotype. These antibodies are specific for epitopes on the human haemoglobin alpha chain (HuHb-alpha). It would appear, therefore, that Hb-2d possesses a CRI that is carried by antibodies to various antigenic determinants on HuHb. The linkage of these different antibodies by the CRI may allow for a common regulatory pathway.

Animals↗

An idiotope expressed on a monoclonal antibody specific for human haemoglobin beta chain and naturally occurring immunoglobulin(s).

HId-1A (gamma 1:kappa), HId-2a (mu:kappa) and HId-4a (gamma 1:kappa) monoclonal anti-idiotopes of BALB/c origin were induced by the human haemoglobin-reactive, B10.D2-derived monoclonal antibody Hb-2d. HId-1a and HId-4a seem to react with the same idiotope and may, in fact, be encoded by the same V, D and J genes. HId-2a, on the other hand, seems to react with an idiotope different from that recognized by the other two anti-Id's and present in the sera of non-immune B10-H-2 congenic mice. HId-2a, but not HId-1a or HId-4a, may react with an idiotope in or near the antigen binding site of Hb-2d. Naturally occurring immunoglobulin carrying the HId-2a idiotope was affinity-purified from the pooled sera of B10-H-2 congenic mice and partially characterized. It possesses primarily the gamma 2b heavy chain, but small amounts of gamma 1, gamma 2a and mu heavy chains are also detectable. The kappa and lambda 1 light chains are both present in significant amounts. In addition, the affinity-purified immunoglobulin is unreactive with human haemoglobin, is not a rheumatoid factor and does not express in detectable amounts the idiotope recognized by HId-1a and HId-4a. It is possible that all or some part of this polyclonal reagent is specific for antigens normally present in the environment.

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AKR/J gene(s) unlinked to H-2 determines dominant inheritance of lymphocyte hyporesponsiveness to acetylcholine receptor.

Mice with the H-2b major histocompatibility complex haplotype are high immune responders to nicotinic acetylcholine receptors (AChR), whereas mice with the H-2k haplotype are generally low responders. F1 progeny of C57BL/6 (H-2b) mice crossed with mice of most H-2k strains are high responders to AChR in standard conditions of testing helper T cell proliferation in vitro (4 X 10(5) lymph node cells/microwell, 1 wk after primary challenge in vivo). In contrast, the F1 progeny of AKR/J (H-2k) crossed with high responder (H-2b) strains (B6, A.BY, or C3H.SW) were all hyporesponsive to AChR when lymphocytes were tested at 4 X 10(5) cells/well. However, at a density of 1 X 10(6) or greater/well, a high level of antigen-specific responsiveness was demonstrable in the F1 hybrid lymphocytes. A shift from low to high responsiveness to AChR at high cell densities was observed also in the H-2b strain AKR.B6. Other strains previously demonstrated to be low responders to AChR did not become responsive to AChR when lymphocyte numbers were increased to 1.4 X 10(6)/well. The N2 generation yielded by backcrossing (AKR X B6)F1 mice to AKR/J were all low responders, whereas N2 progeny derived by backcrossing F1 to B6 were high or low responders in a ratio of approximately 1:1 (independent of their H-2 phenotype). Results consistent with this observation were obtained in (AKR X B6) F2 mice. These data suggest that at least one AKR/J gene outside of the H-2 complex exerts a hyporesponsive influence on the I-A-dependent helper T cell response to AChR in H-2b mice.

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New Thy-1- and H-2-congenic strains of mice and their application in studies on the mechanism of anti-Thy-1.1 response.

The magnitude of the primary humoral anti-Thy-1.1 responses was measured by the number of PFC in spleens of B10.S(7R) mice and some of their H-2 heterozygous F1 hybrids immunized with thymocytes of either AKR.TH or B10.S(7R)-Thy-1a strain. These two of the five newly developed strains are non-H-2 incompatible and non-H-2 compatible with B10.S(7R) mice, respectively. The low anti-Thy-1.1 responses of B10.S(7R) mice and their F1 hybrids after immunization with thymocytes from non-H-2 compatible B10.S(7R)-Thy-1a donors indicated that the I-As "allele" of B10.S(7R) mice and the I-A "alleles" of other parental strains tested did not produce a complementary effect that is required for non-H-2 compatible thymocytes to elicit a good anti-Thy-1 response.

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Immune-response gene-associated antigens (Ia/DR). Structure and function in immunologically related diseases.

Major histocompatibility complex-determined antigens were originally identified as a consequence of their ability to induce rejection of tissue grafts between organisms that are not genetically identical. Currently, much is known about their biochemical nature and intended biological functions. Major histocompatibility complex antigens are found on three types of glycoprotein molecules. One type (class I) is associated with beta 2-microglobulin in the cell-surface membranes of all body tissues and includes H-2K and D molecules in mice and HLA-A, B, and C molecules in humans. These antigens are the major cause of rejection of transplanted organs. The other two types of glycoproteins (class II) are noncovalently linked to each other, are found in the cell-surface membranes of a limited number of cell types, and include H-2-Ia molecules in mice and HLA-DR molecules in humans. They are noted for their ability to elicit graft-versus-host disease. Both class I and class II molecules are, however, important for the immune recognition of pathogens, although the types of responses they modulate are different. Class I molecules are important in the recognition of cell-surface antigens, whereas class II molecules control responsiveness to soluble antigens. Major histcompatibility complex-encoded molecules are also involved in certain autoimmune diseases. As our understanding of major histocompatibility complex-controlled immune responsiveness broadens and hybridoma and gene-cloning technology advances, specific enhancement of desired immune responses and suppression of deleterious ones will most likely become possible.

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Non-H-2 antigens serving as carrier determinants in a primary anti-Thy-1 response in mice.

The primary immune response of mice to the Thy-1 antigens was elicited by intravenous injection of thymocytes from H-2 compatible donors. The magnitude of the ensuing response judged by the number of plaque forming cells producing antibodies lytic for the Thy-1 bearing cells was influenced by some non-H-2 antigens present on the immunizing thymocytes. Absence of non-H-2 incompatibility resulted in a poor response whereas the presence of such an incompatibility allowed a good response. Genetic analysis revealed that the non-H-2 incompatibility affecting the anti-Thy-1 response is controlled by 1-3 independently segregating genes presumably determing molecules acting as carrier determinants for otherwise poorly immunogenic Thy-1 antigens. The carrier effect appeared to be influenced by the gene dosage of the carrier molecules on the immunizing cells. The data presented are discussed in the context of the current concepts of the mechanisms controlling various immune responses.

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Characterization of a monoclonal antibody that recognizes a determinant unique to human haemoglobin beta-chain.

Methodologies are described for the production and characterization of monoclonal antibodies to human haemoglobin. Three monoclonal antibodies are described, two of which recognize distinct determinants on the alpha-chain subunit. A third monoclonal antibody, Hb-2d, recognizes a determinant expressed on human beta-chain. The Hb-2d determinant is shared by human and baboon haemoglobins, but is not expressed by haemoglobins from beef, goose, pig, rabbit, sheep, dog, rat or mouse. Monoclonal antibody Hb-2d will bind to haemoglobin A2 but not to foetal haemoglobin suggesting that delta-but not gamma-chain also expresses the Hb-2d determinant. The results of testing a limited panel of human haemoglobin variants is presented.

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