TY - JOUR
T1 - Mechanisms underlying the formation of the T cell receptor repertoire in rheumatoid arthritis
AU - Walser-Kuntz, Debby R.
AU - Weyand, Cornelia M.
AU - Weaver, Arthur J.
AU - O'fallon, William M.
AU - Goronzy, Jörg J.
N1 - Funding Information:
The authors wish to thank J. W. Fulbrfght for excellent technical assistance, C. Crowson for statistical analysii, T. L. Higgins for manuscript preparation, and Dr. S. Breanndan Moore for providing HlA data. This work was supported in part by the National Institutes of Health (ROI AR41 974 and ROI AR42527) a clinical science grant from the National Arthritis Foundation (AF 14), and the Mayo Foundation.
PY - 1995/6
Y1 - 1995/6
N2 - The contributions of germline-encoded T cell receptor segments and of HLA-DR polymorphisms in shaping the repertoire of human CD4+ CD45RO- T cells were investigated in healthy unrelated Individuals and in patients with rheumatoid arthritis, an HLA-DRB1 *04associated disease. By comparing frequencies of Vβ-Jβ combinations, healthy Individuals segregated into independent clusters, which strongly correlated with the HLA-DRB1 allele expression. The repertoire finger-print imposed by the HLA-DRB1 alleles involved only a selected group of Jβ elements, whereas the distribution of the other Jβ segments was HLA Independent. The HLA-restricted Jβ elements are characterized by a Gly-Pro-Gly sequence within the conserved PheGly-X-Gly motif, which induces rigidity in an otherwise more flexible protein backbone. The T cell receptor repertoire distinguished patients with RA from healthy HLA-DR-matched individuals, suggesting that patients share a selection mechanism that significantly distorts the composition of the T cell receptor repertoire.
AB - The contributions of germline-encoded T cell receptor segments and of HLA-DR polymorphisms in shaping the repertoire of human CD4+ CD45RO- T cells were investigated in healthy unrelated Individuals and in patients with rheumatoid arthritis, an HLA-DRB1 *04associated disease. By comparing frequencies of Vβ-Jβ combinations, healthy Individuals segregated into independent clusters, which strongly correlated with the HLA-DRB1 allele expression. The repertoire finger-print imposed by the HLA-DRB1 alleles involved only a selected group of Jβ elements, whereas the distribution of the other Jβ segments was HLA Independent. The HLA-restricted Jβ elements are characterized by a Gly-Pro-Gly sequence within the conserved PheGly-X-Gly motif, which induces rigidity in an otherwise more flexible protein backbone. The T cell receptor repertoire distinguished patients with RA from healthy HLA-DR-matched individuals, suggesting that patients share a selection mechanism that significantly distorts the composition of the T cell receptor repertoire.
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U2 - 10.1016/1074-7613(95)90004-7
DO - 10.1016/1074-7613(95)90004-7
M3 - Article
C2 - 7796293
AN - SCOPUS:0029004199
SN - 1074-7613
VL - 2
SP - 597
EP - 605
JO - Immunity
JF - Immunity
IS - 6
ER -