T cell receptor gene polymorphisms associated with anti-insulin, autoimmune T cells in diabetes-prone NOD mice

被引:16
作者
Simone, EA [1 ]
Yu, LP [1 ]
Wegmann, DR [1 ]
Eisenbarth, GS [1 ]
机构
[1] UNIV COLORADO,HLTH SCI CTR,BARBARA DAVIS CTR CHILDHOOD DIABET,DENVER,CO 80262
关键词
alpha chain; autoimmunity; insulin; type I diabetes;
D O I
10.1006/jaut.1997.0134
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The great majority of insulin-specific T cell clones isolated from islets of NOD mice react with insulin peptide B-(9-23) (amino acids 9-23 of the insulin B chain). The T cell receptors of these clones contain diverse beta-chains but restricted alpha-chains. The dominant alpha-chain motif is a V alpha 13 segment (10 out of 13) combined to either a J alpha 45 or a J alpha 34 segment (eight out of 13). Furthermore, nine out of 10 of these V alpha 13 segments are a product of a novel NOD TCR V alpha gene which we have termed V alpha 13.3. Analysis of V alpha 13 transcripts from splenic cDNA libraries from the NOD, BALB/c and C57BL/6 mice revealed significant differences between strains. The NOD sequences contained both V alpha 13.1 and the novel V alpha 13.3. The BALB/c contained the previously reported V alpha 13.1 and V alpha 13.2, but not the V alpha 13.3 sequence identified in the NOD anti-insulin T cell clones. The C57BL/6 had V alpha 13.1 and V alpha 13.3 plus two additional novel sequences which we have termed V alpha 13.4 and V alpha 13.5. These V alpha 13 subfamily members differed by two to four amino acids in either the CDR1 region or adjoining the CDR2 region. The frequency of utilization of the different V alpha 13 subtypes varied dramatically between strains. In the NOD spleen, V alpha 13.3 was detected 79% of the time, compared to 21% for V alpha 13.1. In contrast, the C57BL/6 spleen contained only 7% of V alpha 13.3 sequences compared to the other subfamily members present (V alpha 13.1: 27%; V alpha 13.4: 56%; V alpha 23.5: 10%). MHC polymorphisms or other unknown selective pressures may contribute to these differences in V alpha 13 utilization. We hypothesize that the presence and frequent utilization of the V alpha 13.3 T cell receptor element is involved in targeting insulin B-(9-23) and may be related to diabetes susceptibility of NOD mice. (C) 1997 Academic Press Limited.
引用
收藏
页码:317 / 321
页数:5
相关论文
共 29 条
[1]   LIMITED HETEROGENEITY OF T-CELL RECEPTORS FROM LYMPHOCYTES MEDIATING AUTOIMMUNE ENCEPHALOMYELITIS ALLOWS SPECIFIC IMMUNE INTERVENTION [J].
ACHAORBEA, H ;
MITCHELL, DJ ;
TIMMERMANN, L ;
WRAITH, DC ;
TAUSCH, GS ;
WALDOR, MK ;
ZAMVIL, SS ;
MCDEVITT, HO ;
STEINMAN, L .
CELL, 1988, 54 (02) :263-273
[2]   DIVERSITY AND STRUCTURE OF GENES OF THE ALPHA-FAMILY OF MOUSE T-CELL ANTIGEN RECEPTOR [J].
ARDEN, B ;
KLOTZ, JL ;
SIU, G ;
HOOD, LE .
NATURE, 1985, 316 (6031) :783-787
[3]  
Arden Bernhard, 1995, Immunogenetics, V42, P501
[4]   ISLET-SPECIFIC T-CELL CLONES FROM NONOBESE DIABETIC MICE EXPRESS HETEROGENEOUS T-CELL RECEPTORS [J].
CANDEIAS, S ;
KATZ, J ;
BENOIST, C ;
MATHIS, D ;
HASKINS, K .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1991, 88 (14) :6167-6170
[5]   T-CELL RECEPTOR BETA-CHAIN USAGE IN MYELIN BASIC PROTEIN-SPECIFIC RAT LYMPHOCYTES-T [J].
CHLUBA, J ;
STEEG, C ;
BECKER, A ;
WEKERLE, H ;
EPPLEN, JT .
EUROPEAN JOURNAL OF IMMUNOLOGY, 1989, 19 (02) :279-284
[6]   T-CELL RECEPTOR GENES IN AN ALLOREACTIVE CTL CLONE - IMPLICATIONS FOR REARRANGEMENT AND GERMLINE DIVERSITY OF VARIABLE GENE SEGMENTS [J].
CHOU, HS ;
BEHLKE, MA ;
GODAMBE, SA ;
RUSSELL, JH ;
BROOKS, CG ;
LOH, DY .
EMBO JOURNAL, 1986, 5 (09) :2149-2155
[7]   SHARED T-CELL RECEPTOR GENE USAGE IN EXPERIMENTAL ALLERGIC NEURITIS AND ENCEPHALOMYELITIS [J].
CLARK, L ;
HEBERKATZ, E ;
ROSTAMI, A .
ANNALS OF NEUROLOGY, 1992, 31 (06) :587-592
[8]  
DANIEL D, 1995, EUR J IMMUNOL, V25, P1056, DOI 10.1002/eji.1830250430
[9]   Protection of nonobese diabetic mice from diabetes by intranasal or subcutaneous administration of insulin peptide B-(9-23) [J].
Daniel, D ;
Wegmann, DR .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (02) :956-960
[10]  
Dattamajumdar AK, 1996, IMMUNOGENETICS, V44, P432, DOI 10.1007/BF02602804