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Rearrangement of β-chain genes of the T cell antigen receptor in human suppressor T lymphocytes
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Annual AACHT Meeting, 1985 B27 + sibling. These data suggest several possibilities: (1) in Caucasians there are are two different subtypes of B27 and the PvuII 9.2 kb fragment is associated with only one o f the subtypes of the B27 genes; (2) the fragment may be in linkage disequilibrium with only certain B27 genes; and (3) the fragment may be in linkage disequilibrium with certain B7 genes. It is also likely that AS is ;, genetically heterogenous disorder.
REARRANGEMENT OF 3-CHAIN GENES OF THE T CELL ANTIGEN RECEPTOR IN HU~ MAN SUPPRESSOR T LYMPHOCYTES. C. Rohowsky-Kochan, C. Kowal. D.W. King, F.W. Alt, and N. Suciu-Foca; College of Physi~iam and Surgeons of Columbia Universi(v, Ne~ York N Y Specific interactions o f regulatory (helper and suppressor) and effector ~killer~ "l lymphocytes regulate the immune response. Recent studies in mice and in humans have shown that helper and killer T cells rearrange the/3-chain genes of the T cell antigen receptor. Since/3-chain rearrangements have been found in human suppressor clones but not in mice, there is still controversy about the significance o f the B-chain with respect to function. We have analyzed ten mature T cell clones with suppressor function for possible gene rearrangements of the constant region o f the B-chain of the T cell receptor. The T cell clones were derived from different individuals and were generated by in vitro alloactivation of T lymphocytes to distinct HLA-D/DR antigens. Suppressor T cell clones were ascertained by the following criteria: ¢1) ability to inhibit the capacity of resting T cells to induce antibody formation by autologous B cells in the reverse hemolytic plaqueforming cell assay and ELISA: (2) ability to inhibit the MLC response of the original responder and stimulator when tested in the presence o f exogeneous IL2 and/or anti-mycoplasma drug; (3) lack o f T replacing factor production in the presence of IL-2. Both O K T 4 and O K T 8 positive suppressor T cell clones were included in the study. The method of Southern was used to study the rearrangement o f the T cell receptor genes. The hybridization probes included: t aJ Y T C - a 550 base pair fragment of the c D N A clone YT35 which includes the constant region o f the/3-chain gene; (b) J/31 a 4.5 kb genomic clone which contains the functional J/~l gene segments; cc~ J/32 a 4.0 kb EcoR1 fragment containing the J/~2 gene elements. Our results indicate that T cell clones with suppressor activity exhibit gene rearrangement of the 3-chain of the T cell receptor. Either one of the C/3 genes are rearranged in suppressor T cell clones. N o correlation was found between rearrangement o f a particular C gene and cell surface phenotype o f suppressor clones. Our finding that similarly to helper and cytotoxic T cell clones, suppressor clones exhibit rearrangement of/3-chain T-cell receptor genes suggests that the function o f the clones is not encoded by the 3-chain of the T cell receptor.
MOLECULAR CLONING AND STRUCTURE OF A HUMAN INVARIANT CHAIN GENE ENCODING MULTIPLE Ia-ASSOCiATED PROTEIN PRODUCTS. Deirdre O'Sullivan, Dan Larhammar, Per A. Peterson, and Vito Quaranta; Research Institute of Scripps Clinic. La Jolla. CA: and The Wallenburg Laboratory, Uppsala University, Uppsala, Sweden A human gene for the Ia,associated invariant chain was isolated from a genomic library in phage lambda (from T o m Maniatis) and its partial sequence and organization determined. One of three overlapping lambda clones hybridizing to invariant chain c D N A was found to contain the entire gene. The gene is approximately 12 kb long and comprises eight Exons. Its arrangement is ~ery different from that of class II genes, and from that of the immunoglobulin gene
Annual AACHT Meeting, 1985 B27 + sibling. These data suggest several possibilities: (1) in Caucasians there are are two different subtypes of B27 and the PvuII 9.2 kb fragment is associated with only one o f the subtypes of the B27 genes; (2) the fragment may be in linkage disequilibrium with only certain B27 genes; and (3) the fragment may be in linkage disequilibrium with certain B7 genes. It is also likely that AS is ;, genetically heterogenous disorder.
REARRANGEMENT OF 3-CHAIN GENES OF THE T CELL ANTIGEN RECEPTOR IN HU~ MAN SUPPRESSOR T LYMPHOCYTES. C. Rohowsky-Kochan, C. Kowal. D.W. King, F.W. Alt, and N. Suciu-Foca; College of Physi~iam and Surgeons of Columbia Universi(v, Ne~ York N Y Specific interactions o f regulatory (helper and suppressor) and effector ~killer~ "l lymphocytes regulate the immune response. Recent studies in mice and in humans have shown that helper and killer T cells rearrange the/3-chain genes of the T cell antigen receptor. Since/3-chain rearrangements have been found in human suppressor clones but not in mice, there is still controversy about the significance o f the B-chain with respect to function. We have analyzed ten mature T cell clones with suppressor function for possible gene rearrangements of the constant region o f the B-chain of the T cell receptor. The T cell clones were derived from different individuals and were generated by in vitro alloactivation of T lymphocytes to distinct HLA-D/DR antigens. Suppressor T cell clones were ascertained by the following criteria: ¢1) ability to inhibit the capacity of resting T cells to induce antibody formation by autologous B cells in the reverse hemolytic plaqueforming cell assay and ELISA: (2) ability to inhibit the MLC response of the original responder and stimulator when tested in the presence o f exogeneous IL2 and/or anti-mycoplasma drug; (3) lack o f T replacing factor production in the presence of IL-2. Both O K T 4 and O K T 8 positive suppressor T cell clones were included in the study. The method of Southern was used to study the rearrangement o f the T cell receptor genes. The hybridization probes included: t aJ Y T C - a 550 base pair fragment of the c D N A clone YT35 which includes the constant region o f the/3-chain gene; (b) J/31 a 4.5 kb genomic clone which contains the functional J/~l gene segments; cc~ J/32 a 4.0 kb EcoR1 fragment containing the J/~2 gene elements. Our results indicate that T cell clones with suppressor activity exhibit gene rearrangement of the 3-chain of the T cell receptor. Either one of the C/3 genes are rearranged in suppressor T cell clones. N o correlation was found between rearrangement o f a particular C gene and cell surface phenotype o f suppressor clones. Our finding that similarly to helper and cytotoxic T cell clones, suppressor clones exhibit rearrangement of/3-chain T-cell receptor genes suggests that the function o f the clones is not encoded by the 3-chain of the T cell receptor.
MOLECULAR CLONING AND STRUCTURE OF A HUMAN INVARIANT CHAIN GENE ENCODING MULTIPLE Ia-ASSOCiATED PROTEIN PRODUCTS. Deirdre O'Sullivan, Dan Larhammar, Per A. Peterson, and Vito Quaranta; Research Institute of Scripps Clinic. La Jolla. CA: and The Wallenburg Laboratory, Uppsala University, Uppsala, Sweden A human gene for the Ia,associated invariant chain was isolated from a genomic library in phage lambda (from T o m Maniatis) and its partial sequence and organization determined. One of three overlapping lambda clones hybridizing to invariant chain c D N A was found to contain the entire gene. The gene is approximately 12 kb long and comprises eight Exons. Its arrangement is ~ery different from that of class II genes, and from that of the immunoglobulin gene