Assembled DJβ Complexes Influence TCRβ Chain Selection and Peripheral Vβ Repertoire

被引：10

作者：

Carpenter, Andrea C. ^{[1
,2
]}

Yang-Iott, Katherine S. ^{[2
]}

Chao, Linda H. ^{[2
]}

Nuskey, Beth ^{[2
]}

Whitlow, Scott ^{[3
,4
]}

Alt, Frederick W. ^{[3
,4
]}

Bassing, Craig H. ^{[1
,2
]}

机构：

[1] Univ Penn, Immunol Grad Grp, Sch Med, Philadelphia, PA 19104 USA

[2] Univ Penn, Childrens Hosp Philadelphia, Abramson Family Canc Res Inst, Dept Pathol & Lab Med,Sch Med,Ctr Childhood Canc, Philadelphia, PA 19104 USA

[3] Harvard Univ, Childrens Hosp, Howard Hughes Med Inst, Immune Dis Inst,Sch Med, Boston, MA 02115 USA

[4] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA

来源：

JOURNAL OF IMMUNOLOGY | 2009年 / 182卷 / 09期

关键词：

T-CELL-RECEPTOR; RECOMBINATION SIGNAL SEQUENCE; MAJOR HISTOCOMPATIBILITY COMPLEX; CHROMOSOMAL V(D)J RECOMBINATION; CODING-END SEQUENCE; ALLELIC EXCLUSION; IMMATURE THYMOCYTES; GERMLINE TRANSCRIPTION; POSITIVE SELECTION; GENE SEGMENTS;

D O I：

10.4049/jimmunol.0803270

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

TCR beta chain repertoire of peripheral alpha beta T cells is generated through the stepwise assembly and subsequent selection of TCR beta V region exons during thymocyte development. To evaluate the influence of a two-step recombination process on V beta rearrangement and selection, we generated mice with a preassembled D beta 1J beta 1.1 complex on the J beta 1(omega) allele, an endogenous TCRP allele that lacks the D beta 2-J beta 2 cluster, creating the J beta 1(DJ beta) allele. As compared with J beta 1(omega/omega) mice, both J beta 1(DJ beta/omega) and J beta 1(DJ beta/DJ beta) mice exhibited grossly normal thymocyte development and TCR beta allelic exclusion. In addition, V beta rearrangements on J beta 1(DJ beta) and J beta 1(omega) alleles were similarly regulated by TCR beta-mediated feedback regulation. However, in-frame V beta DJ beta rearrangements were present at a higher level on the J beta 1(DJ beta) alleles of J beta 1(DJ beta/omega) alpha beta T cell hybridomas, as compared with on the J beta 1(omega) alleles. This bias was most likely due to both an increased frequency of VP-to-DJ beta rearrangements on J beta 1(DJ beta) alleles and a preferential selection of cells with in-frame V beta DJ beta exons assembled on J beta 1(DJ beta) alleles during the development of J beta 1(DJ beta/omega) alpha beta T cells. Consistent with the differential selection of in-frame V beta DJ beta rearrangements on J beta 1(DJ beta) alleles, the V beta repertoire of alpha beta T cells was significantly altered during alpha beta TCR selection in J beta 1(DJ beta/omega) and J beta 1(DJ beta/DJ beta) mice, as compared with in J beta 1(omega/omega) mice. Our data indicate that the diversity of DJ beta complexes assembled during thymocyte development influences TCR beta chain selection and peripheral VP repertoire. The Journal of Immunology, 2009, 182: 5586-5595.

引用

页码：5586 / 5595

页数：10

共 65 条

[1] Regulation of T cell receptor β gene rearrangements and allelic exclusion by the helix-loop-helix protein, E47 [J].

Agata, Yasutoshi ;

Tamaki, Nobuyuki ;

Sakamoto, Shuji ;

Ikawa, Tomokatsu ;

Masuda, Kyoko ;

Kawamoto, Hiroshi ;

Murre, Cornelis .

IMMUNITY, 2007, 27 (06) :871-884

[2] Thymopoiesis independent of common lymphoid progenitors [J].

Allman, D ;

Sambandam, A ;

Kim, S ;

Miller, JP ;

Pagan, A ;

Well, D ;

Meraz, A ;

Bhandoola, A .

NATURE IMMUNOLOGY, 2003, 4 (02) :168-174

[3] ORDERED REARRANGEMENT OF IMMUNOGLOBULIN HEAVY-CHAIN VARIABLE REGION SEGMENTS [J].

ALT, FW ;

YANCOPOULOS, GD ;

BLACKWELL, TK ;

WOOD, C ;

THOMAS, E ;

BOSS, M ;

COFFMAN, R ;

ROSENBERG, N ;

TONEGAWA, S ;

BALTIMORE, D .

EMBO JOURNAL, 1984, 3 (06) :1209-1219

[4] The CD3-γδε and CD3-ζ/η modules are each essential for allelic exclusion at the T cell receptor β locus but are both dispensable for the initiation of V to (D)J recombination at the T cell receptor-β, -γ, and -δ loci [J].

Ardouin, L ;

Ismaili, J ;

Malissen, B ;

Malissen, M .

JOURNAL OF EXPERIMENTAL MEDICINE, 1998, 187 (01) :105-116

[5] The timing of TCRα expression critically influences T cell development and selection [J].

Baldwin, TA ;

Sandau, MM ;

Jameson, SC ;

Hogquist, KA .

JOURNAL OF EXPERIMENTAL MEDICINE, 2005, 202 (01) :111-121

[6] Recombination signal sequences restrict chromosomal V(D)J recombination beyond the 12/23 rule [J].

Bassing, CH ;

Alt, FW ;

Hughes, MM ;

D'Auteuil, M ;

Wehrly, TD ;

Woodman, BB ;

Gärtner, F ;

White, JM ;

Davidson, L ;

Sleckman, BP .

NATURE, 2000, 405 (6786) :583-586

[7] The mechanism and regulation of chromosomal V(D)J recombination [J].

Bassing, CH ;

Swat, W ;

Alt, FW .

CELL, 2002, 109 :S45-S55

[8] Vβ cluster sequences reduce the frequency of primary Vβ2 and Vβ14 rearrangements [J].

Bassing, Craig H. ;

Whitlow, Scott ;

Mostoslovasky, Raul ;

Yang-Iott, Katherine ;

Ranganath, Sheila ;

Alt, Frederick W. .

EUROPEAN JOURNAL OF IMMUNOLOGY, 2008, 38 (09) :2564-2572

[9] Regulation of V(D)J recombination by nucleosome positioning at recombination signal sequences [J].

Baumann, M ;

Mamais, A ;

McBlane, F ;

Xiao, H ;

Boyes, J .

EMBO JOURNAL, 2003, 22 (19) :5197-5207

[10] Regulation of T cell receptor (TCR) β gene expression by CD3 complex signaling in immature thymocytes:: Implications for TCRβ allelic exclusion [J].

Biro, J ;

Würch, A ;

Potocnik, AJ ;

Falk, I ;

Mossmann, H ;

Eichmann, K .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (07) :3882-3887

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