PMID- 7926306 OWN - NLM STAT- MEDLINE DCOM- 19941108 LR - 20190515 IS - 0012-1797 (Print) IS - 0012-1797 (Linking) VI - 43 IP - 11 DP - 1994 Nov TI - HLA-DQ-restricted, islet-specific T-cell clones of a type I diabetic patient. T-cell receptor sequence similarities to insulitis-inducing T-cells of nonobese diabetic mice. PG - 1318-25 AB - We established a T-cell line and 20 CD4+ T-cell clones from the peripheral blood lymphocytes of a type I diabetic patient using a membrane preparation of a rat insulinoma cell line (beta membrane antigen [BMA]) as a source of antigen. The T-cell line and three selected clones proliferated specifically to stimulation with BMA and to membranes prepared from human islets, rat pancreas, and NOD pancreas, but not to control antigens. Proliferation-inhibition studies using human leukocyte antigen (HLA)-specific monoclonal antibodies revealed HLA-DQw1-restricted recognition of BMA. An analysis of the T-cell receptor (TCR) repertoire of the T-cell line after 8 and 40 days of culture showed a prominent usage of the V alpha 1 and V alpha 12 gene families. Although sequencing of the TCR V alpha and V beta chains of the three clones demonstrated that each used different V alpha and V beta gene segments, structural similarities were found in complementary-determining region 3 (CDR3), the region that is postulated to interact with the peptide component of the TCR ligand. When we compared these TCR sequences with published sequences of disease-inducing T-cells of NOD mice, highly related TCR V beta families were detected. Furthermore, stretches of identical amino acids within the CDR3 region were found between two pairs of human and mouse T-cells. If one considers the species differences in TCR genes and sequence differences in the restriction elements for these cells (HLA-DQ vs. H-2 I-A nod), these sequence similarities are striking and may be useful for pinpointing T-cells of primary importance in the development of disease. FAU - Durinovic-Bello, I AU - Durinovic-Bello I AD - Institute of Diabetes Research, City Hospital Munich-Schwabing, Munich, Germany. FAU - Steinle, A AU - Steinle A FAU - Ziegler, A G AU - Ziegler AG FAU - Schendel, D J AU - Schendel DJ LA - eng SI - GENBANK/S74026 SI - GENBANK/S74027 SI - GENBANK/S74028 PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Diabetes JT - Diabetes JID - 0372763 RN - 0 (HLA-DQ Antigens) RN - 0 (Receptors, Antigen, T-Cell) SB - IM MH - Amino Acid Sequence MH - Animals MH - Base Sequence MH - Cell Line MH - Clone Cells MH - Diabetes Mellitus, Type 1/*genetics/*immunology MH - Female MH - HLA-DQ Antigens/*immunology MH - Humans MH - Islets of Langerhans/*immunology MH - Male MH - Mice MH - Mice, Inbred NOD MH - Molecular Sequence Data MH - Pedigree MH - Receptors, Antigen, T-Cell/*genetics MH - Sequence Homology, Amino Acid MH - T-Lymphocytes/*immunology EDAT- 1994/11/01 00:00 MHDA- 1994/11/01 00:01 CRDT- 1994/11/01 00:00 PHST- 1994/11/01 00:00 [pubmed] PHST- 1994/11/01 00:01 [medline] PHST- 1994/11/01 00:00 [entrez] AID - 10.2337/diab.43.11.1318 [doi] PST - ppublish SO - Diabetes. 1994 Nov;43(11):1318-25. doi: 10.2337/diab.43.11.1318.