CD4 positive peripheral T cells from patients with systemic lupus erythematosus (SLE) are clonally expanded. 2001

W Kolowos, and U S Gaipl, and R E Voll, and C Frank, and J P Haas, and T D Beyer, and J R Kalden, and M Herrmann
Institute of Clinical Immunology, Department of Internal Medicine III, Friedrich-Alexander-University, Erlangen-Nuremberg, Germany.

T cell activation was analysed in peripheral CD4+ T cells from both systemic lupus erythematosus (SLE) patients with active and inactive disease as well as in normal healthy donors (NHD) to investigate the involvement of CD4+ T cells in the etiopathogenesis of SLE. CD4+ T cell receptor (TCR) beta-chain transcripts, containing the complementarity determining region 3 (CDR3), were amplified by reverse transcriptase-polymerase chain reaction (RT-PCR) and analysed by high-resolution polyacrylamide gel electrophoresis. In addition the CDR3 of both clonally activated as well as heterogeneous Vbeta families from SLE patients were analysed at the molecular level. We observed a restricted CDR3 length polymorphism in peripheral CD4+ T cells from SLE patients compared with NHD, more pronounced in patients with high disease activity. Furthermore, in some Vbeta families single peaks in the histogram indicated nearly monoclonal T cell expansion. Sequencing of selected TCR beta-chains revealed a increased content of acidic amino acids in the CDR3 encoded by either proximal Jbeta elements or N nucleotides. We conclude that CD4+ T cells from peripheral blood of SLE patients display features of a secondary antigen driven immune response. The bias of the CDR3 towards acidic amino acids suggests the involvement of positively charged antigens.

UI MeSH Term Description Entries
D008180 Lupus Erythematosus, Systemic A chronic, relapsing, inflammatory, and often febrile multisystemic disorder of connective tissue, characterized principally by involvement of the skin, joints, kidneys, and serosal membranes. It is of unknown etiology, but is thought to represent a failure of the regulatory mechanisms of the autoimmune system. The disease is marked by a wide range of system dysfunctions, an elevated erythrocyte sedimentation rate, and the formation of LE cells in the blood or bone marrow. Libman-Sacks Disease,Lupus Erythematosus Disseminatus,Systemic Lupus Erythematosus,Disease, Libman-Sacks,Libman Sacks Disease
D011110 Polymorphism, Genetic The regular and simultaneous occurrence in a single interbreeding population of two or more discontinuous genotypes. The concept includes differences in genotypes ranging in size from a single nucleotide site (POLYMORPHISM, SINGLE NUCLEOTIDE) to large nucleotide sequences visible at a chromosomal level. Gene Polymorphism,Genetic Polymorphism,Polymorphism (Genetics),Genetic Polymorphisms,Gene Polymorphisms,Polymorphism, Gene,Polymorphisms (Genetics),Polymorphisms, Gene,Polymorphisms, Genetic
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000595 Amino Acid Sequence The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION. Protein Structure, Primary,Amino Acid Sequences,Sequence, Amino Acid,Sequences, Amino Acid,Primary Protein Structure,Primary Protein Structures,Protein Structures, Primary,Structure, Primary Protein,Structures, Primary Protein
D015496 CD4-Positive T-Lymphocytes A critical subpopulation of T-lymphocytes involved in the induction of most immunological functions. The HIV virus has selective tropism for the T4 cell which expresses the CD4 phenotypic marker, a receptor for HIV. In fact, the key element in the profound immunosuppression seen in HIV infection is the depletion of this subset of T-lymphocytes. T4 Cells,T4 Lymphocytes,CD4-Positive Lymphocytes,CD4 Positive T Lymphocytes,CD4-Positive Lymphocyte,CD4-Positive T-Lymphocyte,Lymphocyte, CD4-Positive,Lymphocytes, CD4-Positive,T-Lymphocyte, CD4-Positive,T-Lymphocytes, CD4-Positive,T4 Cell,T4 Lymphocyte
D019674 Genes, T-Cell Receptor beta DNA sequences encoding the beta chain of the T-cell receptor. The genomic organization of the TcR beta genes is essentially the same in all species and is similar to the organization of Ig genes. T-Cell Receptor beta Genes,TcR beta Genes,T-Cell Receptor beta-Chain Genes,Gene, TcR beta,Genes, T Cell Receptor beta,Genes, TcR beta,T Cell Receptor beta Chain Genes,T Cell Receptor beta Genes,TcR beta Gene
D022801 Complementarity Determining Regions Three regions (CDR1; CDR2 and CDR3) of amino acid sequence in the IMMUNOGLOBULIN VARIABLE REGION that are highly divergent. Together the CDRs from the light and heavy immunoglobulin chains form a surface that is complementary to the antigen. These regions are also present in other members of the immunoglobulin superfamily, for example, T-cell receptors (RECEPTORS, ANTIGEN, T-CELL). Complementarity Determining Region,Complementarity Determining Region 1,Complementarity Determining Region 2,Complementarity Determining Region 3,Complementarity Determining Region I,Complementarity Determining Region II,Complementarity Determining Region III,Complementarity-Determining Region,Complementarity-Determining Region 3,Hypervariable Region, Immunoglobulin,Hypervariable Regions, Immunoglobulin,Third Complementarity-Determining Region,Complementarity-Determining Region 3s,Complementarity-Determining Region, Third,Complementarity-Determining Regions,Complementarity-Determining Regions, Third,Immunoglobulin Hypervariable Region,Immunoglobulin Hypervariable Regions,Region, Complementarity Determining,Region, Immunoglobulin Hypervariable,Regions, Complementarity Determining,Regions, Complementarity-Determining,Regions, Immunoglobulin Hypervariable,Third Complementarity Determining Region,Third Complementarity-Determining Regions

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