T CELL RECEPTOR REPERTOIRE AND SUPERANTIGENS IN RHEUMATOID ARTHRITIS
T CELL RECEPTOR REPERTOIRE AND SUPERANTIGENS IN RHEUMATOID ARTHRITIS
批准号:
6275392
负责人:
Brian L Kotzin
金额:
$3.14万
依托单位国家:
美国
项目类别:
财政年份:
1997
资助国家:
美国
项目状态:
已结题
起止时间:
1997-12-01 至 1998-11-30
中文摘要
大量证据表明T细胞在
英文摘要
Considerable evidence indicates that T cells are important in the
immunopathogenesis of rheumatoid arthritis. The major goals of our
current studies are to characterize the T cell receptors (TCRs) expressed
by clonal CD4+ T cell expansions in the synovial fluid of patients with
rheumatoid arthritis and to determine whether these clones are also
present in paired samples of another joint of the same patient and in the
blood. Additional studies will examine whether these clonal expansions
and other specifically expanded T cells are present at later time points.
Finally, the TCRs expressed by these clonal expansions will be expressed
in T cell hybridomas in order to determine the specificity of these T
cells for synovial antigens. In the recent funding period, we have
analyzed TCR b-chain (TCRB) sequences in two joints and blood of an
additional four patients. Despite marked heterogeneity of the synovial T
cell receptor sequences, the results showed that 20-30% of the TCRB
sequences found in one joint were also expressed in a second joint but not
in peripheral blood T cells of the same individual. Analysis of TCRB
complementarity determining region 3 (CDR3) sequences showed the presence
of multiple clonal expansions. The same oligoclonal expansions were
apparent in both joints of the same patient. A few of the expansions were
very large (> 30% of the repertoire within a particular TCRBV subset).
Continued analysis of the TCR b-chain and a-chain repertoire showed
remarkable homology among clones within an individual patient, strongly
suggesting selection by the same synovial antigen. However, we have yet
to find the same or highly homologous TCRs among different patients.
Together, these studies suggest that a significant proportion of synovial
CD4+ T cells have been selected and expanded by conventional antigens in
this disease. Hybridomas expressing RA synovial TCRs have been generated,
and we are currently screening for responses to candidate synovial
antigens and peptides.
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T CELL RECEPTOR REPERTOIRE AND SUPERANTIGENS IN RHEUMATOID ARTHRITIS
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批准号:6566361
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项目类别:
-
资助金额:$19.07万
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财政年份:2000
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负责人:Brian L Kotzin
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依托单位:
T CELL RECEPTOR REPERTOIRE AND SUPERANTIGENS IN RHEUMATOID ARTHRITIS
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批准号:6504509
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项目类别:
-
资助金额:$19.07万
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财政年份:2000
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负责人:Brian L Kotzin
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依托单位:
DENVER AUTOIMMUNITY CENTER OF EXCELLENCE
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批准号:6170707
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项目类别:
-
资助金额:$231.82万
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财政年份:1999
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负责人:Brian L Kotzin
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依托单位:
AUTOIMMUNITY CENTER OF EXCELLENCE
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批准号:6021948
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项目类别:
-
资助金额:$125.2万
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财政年份:1999
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负责人:Brian L Kotzin
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依托单位:
DENVER AUTOIMMUNITY CENTER OF EXCELLENCE
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批准号:6534210
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项目类别:
-
资助金额:$245.93万
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财政年份:1999
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负责人:Brian L Kotzin
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依托单位:
Denver Autoimmunity Center of Excellence
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批准号:6685600
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项目类别:
-
资助金额:$0.0万
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财政年份:1999
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负责人:Brian L Kotzin
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依托单位:
DENVER AUTOIMMUNITY CENTER OF EXCELLENCE
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批准号:6374322
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项目类别:
-
资助金额:$238.77万
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财政年份:1999
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负责人:Brian L Kotzin
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依托单位:
T CELL RECEPTOR REPERTOIRE AND SUPERANTIGENS IN RHEUMATOID ARTHRITIS
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批准号:6304253
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项目类别:
-
资助金额:$3.22万
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财政年份:1999
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负责人:Brian L Kotzin
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依托单位:
CD4+T CELL EXPANSIONS IN HIV
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批准号:2887951
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项目类别:
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资助金额:$22.35万
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财政年份:1998
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负责人:Brian L Kotzin
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依托单位:
CD4+T CELL EXPANSIONS IN HIV
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批准号:2802466
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项目类别:
-
资助金额:$22.35万
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财政年份:1998
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负责人:Brian L Kotzin
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依托单位:
PATHOGENIC T CELLS IN CHRONIC BERYLLIUM DISEASE
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批准号:6390308
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项目类别:
-
资助金额:$22.71万
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财政年份:1998
-
负责人:Brian L Kotzin
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依托单位:
PATHOGENIC T CELLS IN CHRONIC BERYLLIUM DISEASE
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批准号:6184654
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项目类别:
-
资助金额:$22.28万
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财政年份:1998
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负责人:Brian L Kotzin
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依托单位:
PATHOGENIC T CELLS IN CHRONIC BERYLLIUM DISEASE
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批准号:6537560
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项目类别:
-
资助金额:$23.15万
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财政年份:1998
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负责人:Brian L Kotzin
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依托单位:
Pathogenic T Cells in Chronic Beryllium Disease
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批准号:6685352
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项目类别:
-
资助金额:$33.95万
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财政年份:1998
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负责人:Brian L Kotzin
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依托单位:
PATHOGENIC T CELLS IN CHRONIC BERYLLIUM DISEASE
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批准号:6030946
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项目类别:
-
资助金额:$21.86万
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财政年份:1998
-
负责人:Brian L Kotzin
-
依托单位:
T CELL RECEPTOR REPERTOIRE AND SUPERANTIGENS IN RHEUMATOID ARTHRITIS
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批准号:6114157
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项目类别:
-
资助金额:$3.22万
-
财政年份:1998
-
负责人:Brian L Kotzin
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依托单位:
PATHOGENIC T CELLS IN CHRONIC BERYLLIUM DISEASE
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批准号:2831974
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项目类别:
-
资助金额:$22.32万
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财政年份:1998
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负责人:Brian L Kotzin
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依托单位:
T CELL RECEPTOR REPERTOIRE AND SUPERANTIGENS IN RHEUMATOID ARTHRITIS
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批准号:6245293
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项目类别:
-
资助金额:$2.65万
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财政年份:1997
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负责人:Brian L Kotzin
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依托单位:
FASEB RESEARCH CONFERENCE ON AUTOIMMUNITY
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批准号:2074342
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项目类别:
-
资助金额:$1.2万
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财政年份:1995
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负责人:Brian L Kotzin
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依托单位:
IMMUNOLOGICAL SCIENCES STUDY SECTION
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批准号:3554902
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项目类别:
-
资助金额:$3.29万
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财政年份:1990
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负责人:Brian L Kotzin
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依托单位:
海外基金