ライフサイエンスコーパス: TCRalpha

1 pared with that of B6.Sle1 and B6.muMT or B6.Tcralpha(-/-).

2 e TCRdelta gene assembly, while most are for TCRalpha.

3 iated autoantigens in the context of diverse TCRalpha.

4 vo for ability to process the ERAD substrate TCRalpha.

5 program of expression different from that of TCRalpha.

6 gh the exclusive use of a TRAV1-2-containing TCRalpha.

7 intact TCRbeta-chain and in association with TCRalpha.

8 rised 12% of circulating CD8(+) T cells, and TCRalpha analysis revealed two distinct co-expressed TCR

9 ified, through global T-cell receptor alpha (TCRalpha) analysis, an invariant TCRValpha21 sequence, w

10 Detailed analysis of TCRalpha and -beta chain composition is consistent with

11 We bred NOD mice hemizygous at both TCRalpha and beta (TCRalpha(+/-) beta(+/-)) loci, render

12 for preference in the V segments used in the TCRalpha and beta genes.

13 nage the separate regulatory programs of the TCRalpha and Dad1 genes.

14 rangement of the T cell receptor (TCR) genes TCRalpha and delta is specifically regulated by a comple

15 However, our understanding of complementary TCRalpha and TCRbeta chain utilization is very limited f

16 Characterizing the TCRalpha and TCRbeta chains expressed by T cells respond

17 us amplification of transcripts encoding the TCRalpha and TCRbeta chains from single cells.

18 lones were used to isolate cDNA encoding the TCRalpha and TCRbeta chains that recognize the Kd54-68/I

19 ertoire analysis with paired coexpression of TCRalpha and TCRbeta chains with single-cell resolution.

20 juxtaposed hypervariable CDR3 regions on the TCRalpha and TCRbeta chains, and obtaining the paired se

21 This method involves sequencing of TCRalpha and TCRbeta genes, and amplifying functional ge

22 equires the expression of both prerearranged TCRalpha and TCRbeta genes, indicating a critical role f

23 timing and sequence of rearrangements of the TCRalpha and TCRbeta loci in adult murine thymic precurs

24 these beads can be used to capture and pair TCRalpha and TCRbeta sequences from total T-cell RNA, en

25 LB/c bone marrow and spleen cells expressing TCRalpha and TCRbeta transgenes that recognize CD1d.

26 ondelta/gamma can assemble with both chicken TCRalpha and TCRbeta via conserved polar transmembrane s

27 Assembly of TCRalpha and TCRdelta genes from the TCRalpha/delta locu

28 xpression in the thymus with the result that TCRalpha and TCRgamma proteins are not expressed in the

29 gnaling module is known to require one basic TCRalpha and two zetazeta aspartic acid TM residues.

30 at5b transgene-mediated lymphoma occurred on TCRalpha(-/-) and pre-TCRalpha(-/-) backgrounds.

31 Egr3 transgenic mice have poor expression of TCRalpha, and based on the predominant usage of 3' Valph

32 TCRs due to incomplete allelic exclusion of TCRalpha, and we hypothesized they are highly alloreacti

33 These changes in clonal composition were TCRalpha- and beta chain-dependent and were directly rel

34 ng a deep-sequencing approach, we determined TCRalpha- and TCRbeta-chain usage, as well as alphabetaT

35 We identified 15 TCRbeta and 4 TCRalpha antigen receptor sequences shared between psori

36 mbled alpha subunits of the T cell receptor (TCRalpha) are degraded by proteasomes following their di

37 ntrinsic to the pre-TCR, which are absent in TCRalpha, are essential for its unique function.

38 decreased in the absence of pre-Talpha on a TCRalpha(-/-) background.

39 d lymphoma occurred on TCRalpha(-/-) and pre-TCRalpha(-/-) backgrounds.

40 D mice hemizygous at both TCRalpha and beta (TCRalpha(+/-) beta(+/-)) loci, rendering them incapable

41 y develop chronic colitis mediated by CD4(+) TCRalpha(-)beta(+) T cells.

42 Surprisingly, we were able to detect TCRalpha, beta, and delta mRNA transcribed from loci tha

43 Rmu transcripts relative to the conventional TCRalpha, beta, gamma, and delta mRNA during postnatal d

44 avalin A-induced proliferation, but not anti-TcRalpha/beta induced proliferation, of mouse lymph node

45 at are Thy1+,B220+,CD4+,CD8-, express either TCRalpha/beta or TCRgamma/delta, and produce mainly type

46 es of PN mice were CD4+ and expressed either TCRalpha/beta or TCRgamma/delta.

47 s expressing high affinity T-cell receptors (TCRalpha/beta) for the melanoma antigen MART-1/HLA-A*020

48 L/lpr mice, most of which were CD4-,CD8- and TCRalpha/beta+, the majority of the Thy1+,B220+ T cells

49 ly in-frame, but often aberrant, with clonal TCRalpha but no comparable clonal TCRbeta rearrangement,

50 degradation (ERAD) substrates, CD3delta and TCRalpha, but does not alter levels of several non-ERAD

51 Examination of mice heterozygous for TRAC (TCRalpha(+/-)), capable of only one functional TCRalpha

52 xtends into the membrane-proximal domains of TCRalpha-CD3deltaepsilon and TCRbeta-CD3gammaepsilon.

53 assembly, consistent with membrane-proximal TCRalpha-CD3deltaepsilon interactions.

54 vestigated the structure and assembly of the TCRalpha-CD3epsilon-CD3delta transmembrane domains both

55 ta segments and the five CD3epsilon-CD3delta-TCRalpha-CD3zeta-CD3zeta segments, are presumably center

56 animals, we directly evaluate the extent of TCRalpha CDR3 diversity and the pMHCII binding attribute

57 fferent TCRbeta-chains but sharing identical TCRalpha CDR3 loops displayed identical functional speci

58 to their allogeneic ligand as compared with TCRalpha(+/-) cells, suggesting increased breadth in pep

59 The pre-TCR complex (TCRbeta-pre-TCRalpha chain (pTalpha)), first expressed in a fraction

60 pecific to the cytoplasmic domain of the pre-TCRalpha chain (pTalpha).

61 enerated transgenic mice expressing only the TCRalpha chain (Valpha19i) that defines MAIT cells.

62 How cells expressing an invariant TCRalpha chain and a restricted set of TCRbeta chains re

63 iting, whereas replacement of the transgenic TCRalpha chain by ongoing gene rearrangement occurred in

64 tive T reg and T conv cells express a second TCRalpha chain derived from endogenous loci.

65 These cells then need to generate a TCRalpha chain gene encoding a TCRalpha chain, which, wh

66 ch replacement occurs through the process of TCRalpha chain gene revision whereby a Valpha gene segme

67 ity of developing thymocytes to revise their TCRalpha chain genes.

68 th a limited capacity to undergo revision of TCRalpha chain genes.

69 repertoire with a fixed TCRbeta chain and a TCRalpha chain minilocus.

70 ct CD1d-restricted T cells bearing different TCRalpha chain rearrangements.

71 s certain NK cell receptors and an invariant TCRalpha chain specific for the MHC class I-like CD1d pr

72 eral TCRbeta chains paired with a transgenic TCRalpha chain to produce a TCR with higher affinity tha

73 Deep sequencing of millions of TCRalpha chain transcripts revealed that the TCR reperto

74 ature of MR1 in conjunction with biased MAIT TCRalpha chain usage is widely thought to indicate limit

75 ansgenic TCRbeta chain, but do not express a TCRalpha chain, and, by a number of phenotypic and molec

76 re "innate" T cells that express a canonical TCRalpha chain, have a memory phenotype, and rapidly sec

77 T-cell population, enriched in an invariant TCRalpha chain, is expanded in PNH patients and may be r

78 to generate a TCRalpha chain gene encoding a TCRalpha chain, which, when paired with the TCRbeta chai

79 at least two subsets: type I, semi-invariant TCRalpha chain-expressing (Valpha14Jalpha18 in mice, Val

80 24Jalpha18 in humans), and type II, variable TCRalpha chain-expressing.

81 , like most NK T cells, express an invariant TCRalpha chain.

82 l, we now introduced the human invariant NKT TCRalpha-chain (Valpha24Jalpha18) into the hCD1d-knockin

83 hocytes, NKT cells that express an invariant TCRalpha-chain and recognize lipid Ags presented by the

84 sive usage of the invariant Valpha14Jalpha18 TCRalpha-chain and their innate-like effector function.

85 promoters such as the TEA promoter to drive TCRalpha-chain gene assembly in these cells.

86 CD8(-) (double negative (DN)) thymocytes and TCRalpha-chain genes are assembled in CD4(+)CD8(+) (doub

87 important, because the premature assembly of TCRalpha-chain genes in DN thymocytes would disrupt alph

88 ement in CD4(+)CD8(+) thymocytes to form the TCRalpha-chain of the alphabeta TCR.

89 cells, this population has a highly diverse TCRalpha-chain repertoire.

90 TCRalpha-chain sequence analysis showed that clones that

91 In this study, we used fixed TRAV8-1/TRAJ9 TCRalpha-chain transgenic mice to assess the impact of P

92 odies specific for variable regions of mouse TCRalpha chains and the need for prior knowledge of vari

93 ymocytes rearrange and express two different TCRalpha chains and, thus, display two alphabetaTCRs on

94 We find by sequencing of TRAV14 (Valpha2) TCRalpha chains associated with a transgenic TCRbeta cha

95 ed VJalpha rearrangements that do not encode TCRalpha chains capable of forming selectable alphabeta

96 alpha recombination and that the majority of TCRalpha chains expressed in mature T cells are products

97 uired both for dislocation and for targeting TCRalpha chains to the proteasome.

98 raction of their Valpha14-Jalpha18 invariant TCRalpha chains with CD1d expressed on double-positive (

99 ng 'invariant' T cell receptor alpha-chains (TCRalpha chains) containing variable (V) and joining (J)

100 - and CDR3beta-sharing, cells expressing two TCRalpha chains, and multiple forms of sequencing error.

101 analysis revealed two distinct co-expressed TCRalpha chains, with only one contributing to binding o

102 by additional contacts formed by endogenous TCRalpha chains.

103 consisting of the 2C TCRbeta and endogenous TCRalpha chains.

104 HC) binding modes when paired with different TCRalpha chains.

105 mmon transgenic TCRbeta-chain and endogenous TCRalpha-chains.

106 possess cross-reactive TCRs with endogenous TCRalpha-chains; MHC-mismatched H-2(b) but not matched H

107 In the absence of ATM, delayed TCRalpha coding joint formation results both in a reduct

108 mmunoglobulin domains, but shortening of the TCRalpha connecting peptide reduced assembly, consistent

109 re-TCR expressed on double-positive cells in TCRalpha-deficient (TCRalpha(-/-)) mice produced a small

110 biquitination on lysines is not required for TCRalpha degradation by the proteasome.

111 (which are exclusively enhancer driven) and TCRalpha/delta (which use an enhancer-independent crypti

112 as the Vdelta5 gene segment on the wild-type TCRalpha/delta allele.

113 , amplifications and deletions involving the Tcralpha/delta and Igh loci.

114 lta locus is nonsyntenic to the conventional TCRalpha/delta and is unusual in that the V genes are mo

115 d restriction on the variable gene usage for TCRalpha/delta gene assembly plays an important role in

116 e use gene targeting to construct a modified TCRalpha/delta locus (TCRalpha/delta(5DeltaT)) in which

117 is required for normal rearrangement of the Tcralpha/delta locus but not for V(D)J recombination at

118 Rather the finch's conventional TCRalpha/delta locus contains VH genes that are expresse

119 pically acquire translocations involving the Tcralpha/delta locus during V(D)J recombination, and ins

120 (Rag2(c/c) mice) show dramatic disruption of Tcralpha/delta locus integrity.

121 mbly of TCRalpha and TCRdelta genes from the TCRalpha/delta locus is tightly controlled for the prope

122 tions, suggesting that rearrangements at the Tcralpha/delta locus occur early during tumor developmen

123 Of >100 shared variable gene segments in the TCRalpha/delta locus, only a few are predominantly used

124 ppears to be associated with position in the TCRalpha/delta locus.

125 ain genes lie in a single complex locus, the TCRalpha/delta locus.

126 the present study, screening for TCRbeta and TCRalpha/delta translocations by FISH and ligation-media

127 mocytes die of TCR-beta(-) tumors containing Tcralpha/delta translocations, other clonal translocatio

128 o construct a modified TCRalpha/delta locus (TCRalpha/delta(5DeltaT)) in which the TEA promoter lies

129 14) between the T-cell receptor alpha/delta (TCRalpha/delta) and immunoglobulin H loci, but the molec

130 precisely at the T-cell receptoralpha/delta (Tcralpha/delta) locus, suggesting the involvement of V(D

131 thymic lymphomas with clonal chromosome 14 (TCRalpha/delta) translocations.

132 tment of preleukemic Pten-null mice prevents Tcralpha/delta-c-myc translocation and leukemia stem cel

133 (D)J] recombination completely abolishes the Tcralpha/delta-c-myc translocation and T-ALL development

134 )CD8(-) to CD4(+)CD8(+), the stage where the Tcralpha/delta-c-myc translocation occurs.

135 t with their target site, namely, the TMD of TCRalpha, designated CP.

136 TCRdelta diversity and indirectly regulated TCRalpha diversity.

137 in marrow transplants from either CD8-/- or TCRalpha-/- donors failed to eliminate malignant and nor

138 s restored in the recipient B-cell-deficient TCRalpha double knockout (alphamicroDKO) mice by the tra

139 ch more severe colitis in IL-12p35-deficient TCRalpha double knockout (alphap35DKO) mice compared wit

140 litis in TCRalphaKO mice, IL-12p35-deficient TCRalpha double knockout mice were generated.

141 or the mechanism(s) governing this selective TCRalpha down-regulation, we present evidence for the ro

142 TCRbeta paired with endogenously rearranged TCRalpha endowed unprimed T cells with autoantigen react

143 This developmental event is regulated by the TCRalpha enhancer (Ealpha), which induces chromatin modi

144 these factors are recruited by ETS-1 to the TCRalpha enhancer and actively repress differentiation.

145 tage-specific activities of the TCRdelta and TCRalpha enhancers (Edelta and Ealpha), respectively.

146 Molecularly, this monospecificity was due to TCRalpha exclusion: one transgenic TCRalpha protein was

147 n locus, which ensured appropriate timing of TCRalpha expression and allowed secondary rearrangements

148 nd 5' Jalpha gene segments, the low level of TCRalpha expression is a result of DP death soon after t

149 ogation of TCRalpha/gamma exclusion by early TCRalpha expression results in the formation of isotypic

150 We found that the lack of dual TCRalpha expression skewed the insulin-specific thymocyt

151 ransgenic receptors as a consequence of dual TCRalpha expression.

152 ation perfectly correlated with targeting of TCRalpha for ERAD.

153 CD4(+) T cells from immunized 3.L2beta(+/-) TCRalpha(+/-) Foxp3(EGFP) mice were restimulated in cult

154 Thus, abrogation of TCRalpha/gamma exclusion by early TCRalpha expression re

155 Such "TCRalpha/gamma exclusion" is a feature of normal thymocy

156 mune receptor chains (VH+VL or TCRbeta/delta+TCRalpha/gamma) at the single-cell level for typical sam

157 gene regulatory mechanisms are acting on the TCRalpha gene in peripheral T cells to ensure its high l

158 cell-conditional ablation of TRIM28 impaired TCRalpha gene rearrangement and compromised the developm

159 that coincides with the onset of endogenous TCRalpha gene rearrangement and expression.

160 A sparse population of thymocytes undergoes TCRalpha gene rearrangement early in development, before

161 itions, thymocytes appear to undergo further TCRalpha gene rearrangement to produce a receptor that m

162 PS-induced thymus weight loss and stimulated TCRalpha gene rearrangement.

163 l development, and by modulating TCRbeta and TCRalpha gene segment utilization.

164 ene loci, including one between the TCRdelta/TCRalpha gene segments and the ubiquitously expressed Da

165 In the RAG+ background, where endogenous TCRalpha genes are rearranged and expressed, CD4+ 2C T c

166 Comparison of the TCRalpha genes expressed in wild-type or mutant mice sho

167 Retroviral expression of TCRalpha genes in TCR transgenic RAG-deficient T cells r

168 ion, T cell-deficient mice (T-cell receptor, TCRalpha(-/-)) had preserved LV systolic and diastolic f

169 Remarkably, TCRalpha has a cytosolic tail of only five amino acid re

170 amatically when in competition with pTalpha, TCRalpha induced defective proliferation, survival, and

171 lpha-subunit of the T-cell antigen receptor (TCRalpha) into the alpha-helical transmembrane domain of

172 e T-cell antigen receptor (TCR) alpha-chain (TCRalpha) is a type I integral membrane protein that bec

173 The gene for T-cell receptor alpha chain (TCRalpha) is exclusively expressed in T cells, and the c

174 one expects to find in-frame, self-reactive TCRalpha joins on TCR excision circles (TRECs), which ar

175 We previously demonstrated that a variant of TCRalpha lacking lysines (KalphaR) is degraded by this p

176 Surprisingly, TCRalpha LCR activity appears to decrease in peripheral

177 type specificity and developmental timing of TCRalpha LCR activity are both still unknown.

178 In this study we report the activation of TCRalpha LCR activity at the CD4-CD8-CD25-CD44- stage of

179 ate that they function to maintain an active TCRalpha LCR assembly in vivo.

180 The TCRalpha LCR contains a CTCF-dependent and multiple CTCF

181 e established a transgenic reporter model of TCRalpha LCR function that allows for analysis of LCR ac

182 he position-effect suppression region of the TCRalpha LCR harbors an array of CTCF-independent, posit

183 s on DNase hypersensitive site (HS) 6 of the TCRalpha LCR.

184 reliably reproduce a developmentally correct TCRalpha-like expression pattern during thymic developme

185 quence of simultaneous rearrangement of both TCRalpha loci.

186 ing approach was used to generate a modified TCRalpha locus (TCRalpha(sJ)) with a limited capacity to

187 Phenotypic allelic exclusion at the TCRalpha locus is developmentally regulated in thymocyte

188 Allelic exclusion is inefficient at the TCRalpha locus, allowing a sizeable portion of T cells t

189 ion in the Ealpha and distant regions of the TCRalpha locus, coupled with recruitment of Rag proteins

190 open chromosomal DNA breaks, predisposing to TCRalpha locus-associated chromosomal abnormalities.

191 enomic instability, frequently affecting the TCRalpha locus.

192 oducts of secondary V/J recombination in the TCRalpha locus.

193 and V(D)J recombination is initiated at the TCRalpha locus.

194 ial chromatin configurations observed at the TCRalpha locus.

195 ediated active chromatin modification in the TCRalpha locus.

196 The TCRdelta locus is contained within the TCRalpha locus; TCRalpha variable region exons are encod

197 TCRalpha -/- mice lack the alpha chain of the T-cell rec

198 Likewise, TCRalpha -/- mice were not protected against ischemic AR

199 nd 2) T-cell receptor alpha-chain deficient (TCRalpha -/-) mice.

200 gen and alloantigen peptide-MHC tetramers in TCRalpha(+/-) mice.

201 In addition, Notch activity alone in TCRalpha(-) mice can induce the up-regulation of HES1, s

202 the development of CD8 lineage thymocytes in TCRalpha(-) mice in which TCR/MHC engagement cannot occu

203 pearance of mature CD8 lineage thymocytes in TCRalpha(-) mice.

204 amined in the lymphoid tissues and colons of TCRalpha(-/-) mice and interleukin 4-deficient TCRalpha(

205 TCRalpha(-/-) mice exposed to CO or treated with the pha

206 rease of CD8(+) T cells was also observed in TCRalpha(-/-) mice overexpressing Egr-1, which lowers th

207 Culture of polyclonal T cells from young TCRalpha(-/-) mice with colonic epithelial cells under T

208 high levels of anti-ssDNA IgM Abs in B6.Sle1.Tcralpha(-/-) mice, and had an increased expression of a

209 HO-1 induction ameliorated active colitis in TCRalpha(-/-) mice, and therapeutic effects correlated w

210 diseased colon and appendix (cecal patch) of TCRalpha(-/-) mice, but not germfree TCRalpha(-/-) mice.

211 In the TCRalpha(-/-) mice, the development of colitis is associ

212 tch) of TCRalpha(-/-) mice, but not germfree TCRalpha(-/-) mice.

213 Ralpha(-/-) mice and interleukin 4-deficient TCRalpha(-/-) mice.

214 ty to induce L-SAT after transfer to SCID or TCRalpha(-/-) mice.

215 double-positive cells in TCRalpha-deficient (TCRalpha(-/-)) mice produced a small number of mature CD

216 T-cell receptor alpha mutant (TCRalpha(-/-)) mice spontaneously develop chronic coliti

217 kout (Jalpha18(-/-)) and NKT cell-deficient (TCRalpha(-/-)) mice, which express CD1d but are deficien

218 c epithelial cells was markedly increased in TCRalpha-/- mice and IFN-gamma-/- x TCRalpha-/- mice com

219 eased in TCRalpha-/- mice and IFN-gamma-/- x TCRalpha-/- mice compared with IL-4(-/-) x TCRalpha-/- m

220 In contrast, IFN-gamma-/- x TCRalpha-/- mice developed colitis similar to that prese

221 developed colitis similar to that present in TCRalpha-/- mice.

222 epithelial cell proliferation in IL-4(-/-) x TCRalpha-/- mice.

223 ortant role in the development of colitis in TCRalpha-/- mice.

224 x TCRalpha-/- mice compared with IL-4(-/-) x TCRalpha-/- mice.

225 ned by creating IL-4- or IFN-gamma-deficient TCRalpha-/- mice.

226 ears to decrease in peripheral T cells where TCRalpha mRNA is normally up-regulated.

227 CD3deltaepsilon assembled with a TCRalpha mutant that lacked both immunoglobulin domains,

228 s in B or T cells, we have bred the muMT and Tcralpha(-/-) mutations onto B6.Sle1 resulting in the ab

229 recombinatorial biases, a small fraction of TCRalpha or beta-chains are shared by most individuals,

230 f mAbs specific for mouse TCRbeta (H57-597), TCRalpha or CD3 promptly reduced the number of CD4(+) an

231 ecificity of Valpha14+ T cells, we conducted TCRalpha or TCRbeta chain transduction experiments.

232 , degradation of proteins from the ER, using TCRalpha or US11-mediated degradation of class I major h

233 ach line uses the invariant Valpha14Jalpha18 TCRalpha paired with unique Vbeta7 or Vbeta8.2 subunits.

234 Here, we express TCRalpha precisely at the pre-TCR checkpoint, at levels

235 to select NK1.1+ T cells can originate from TCRalpha-/- precursors but not from TCRbeta-/- precursor

236 However, Edelta is unable to function with TCRalpha promoters such as the TEA promoter to drive TCR

237 as due to TCRalpha exclusion: one transgenic TCRalpha protein was selectively down-regulated from the

238 c mice, which prematurely express transgenic TCRalpha proteins in early double-negative (DN) thymocyt

239 We report here that early expression of TCRalpha proteins results in the formation of TCRalphaga

240 at levels resembling those of endogenous pre-TCRalpha (pTalpha), and in the absence of endogenous pTa

241 antigen receptors (TCRs) comprising a unique TCRalpha rearrangement between the Trav11 and Traj18 gen

242 By analyzing TCRalpha rearrangement in orphan nuclear receptor RORgam

243 TCRalpha rearrangement is restricted to the 5' end of th

244 ily conserved T cells with another invariant TCRalpha rearrangement was recently characterized.

245 Ralpha(+/-)), capable of only one functional TCRalpha rearrangement, demonstrated a defect in generat

246 ors that are normally assembled by secondary TCRalpha rearrangement.

247 s expressed the invariant Valpha14-Jalpha281 TCRalpha rearrangement.

248 T-cell receptor-alpha (TCRalpha) rearrangement in CD4(+)CD8(+) double-positive

249 ional programs that control Valpha14Jalpha18 TCRalpha rearrangements and the population size of iNKT

250 gements, we developed a mouse model in which TCRalpha rearrangements are restricted to the double-neg

251 ed fraction of T cells containing productive TCRalpha rearrangements on both alleles can be explained

252 fractions of cells containing two productive TCRalpha rearrangements, did not sufficiently account fo

253 the original TCRTg specificity by endogenous TCRalpha rearrangements, indicating that TCR signals mus

254 cell pool by cells that have undergone early TCRalpha rearrangements.

255 ult of DP death soon after the initiation of TCRalpha rearrangements.

256 -/-) T cells into TCRalpha(-/-) vs ICAM(-/-)/TCRalpha(-/-) recipient animals.

257 gammadelta T cells in the TCRalpha(-/-) recipients of scurfy cells markedly expand

258 A high frequency of scurfy T cells in TCRalpha(-/-) recipients produced IL-10, suggesting that

259 In this study, we show that TCRalpha(-/-) recipients, which lack alphabeta T cells b

260 ally rejected by the majority of ICAM-1(-/-)/TCRalpha(-/-) recipients.

261 r cytokine production from scurfy T cells in TCRalpha(-/-) recipients.

262 d thymocyte survival by bcl-2 cannot improve TCRalpha recombination and T cell development.

263 recombination but is essential for secondary TCRalpha recombination and that the majority of TCRalpha

264 D8(+) thymocytes is not required for initial TCRalpha recombination but is essential for secondary TC

265 pha enhancer is active in T cells and drives TCRalpha recombination in collaboration with a locus con

266 uster and there is little apparent secondary TCRalpha recombination.

267 g a human CD25 reporter under control of pre-TCRalpha regulatory elements almost exclusively have the

268 premature apoptosis, resulting in a limited Tcralpha repertoire biased toward 5' Jalpha segment usag

269 hus allowing a comprehensive analysis of the TCRalpha repertoire in a relatively large cohort of mice

270 Thus, T cells expressing a TCRalpha repertoire that is the product of early gene re

271 +) T cells that develop are limited in their TCRalpha repertoire, preferentially using early rearrang

272 Moreover, although most contribute to the TCRalpha repertoire, variable gene segments that are Jal

273 Disruption of this loop also narrowed the TCRalpha repertoire, which, we believe, followed as a co

274 r positive selection, thereby regulating the TCRalpha repertoire.

275 n and a highly public T cell receptor alpha (TCRalpha) repertoire in the MAIT cell compartment withou

276 cell compartment, though deep sequencing of TCRalpha repertoires of dual TCR T cells and TCRalpha(+/

277 to generate diverse TCRdelta repertoires and TCRalpha repertoires, respectively.

278 lphabeta T cells in B6.Sle1.muMT and B6.Sle1.Tcralpha(-/-), respectively.

279 ents of isolated T cell receptors (TCR) from TCRalpha retrogenic mice with autoimmune encephalomyelit

280 inding and crystallography showed linkage of TCRalpha sequence motifs to high-affinity recognition of

281 ng a fixed Tg TCR beta-chain, the associated TCRalpha sequences in wild-type and PLZF-Tg mice overlap

282 T-cell isolates were shown to contain TCRalpha signal ends from chromosome 14 inserted into th

283 Thymocytes from mice homozygous for the TCRalpha(sJ) allele are defective in their ability to ge

284 used to generate a modified TCRalpha locus (TCRalpha(sJ)) with a limited capacity to undergo revisio

285 shed capacity to be positively selected, and TCRalpha(sJ/sJ) mice have significantly reduced numbers

286 TCRalpha repertoires of dual TCR T cells and TCRalpha(+/-) T cells demonstrated unique TCRs in the pr

287 Cells were found to express TCRalpha, TCRbeta, CD152 (CTLA-4), CD154 (CD40L), T-bet,

288 ested that a hydrophobic patch created after TCRalpha-TCRbeta pairing has a role in maintaining the c

289 pproach retains information about individual TCRalpha-TCRbeta pairs, TCRs of interest can be expresse

290 The mouse TCRalpha/TCRdelta/Dad1 gene locus bears a locus control

291 by increasing the hydrophobic nature of the TCRalpha TM region.

292 ved serine residues in the cytosolic tail of TCRalpha to alanine decreased ubiquitination, whereas pl

293 endent, HRD1-mediated ubiquitination targets TCRalpha to the ERAD pathway.

294 d levels of the canonical Valpha14-Jalpha281 TCRalpha transcript seen in NK T cells.

295 Substitution of TCRalpha transmembrane and cytoplasmic domains with thos

296 TCRalpha variable gene (TRAV) gene usage was more divers

297 ocus is contained within the TCRalpha locus; TCRalpha variable region exons are encoded by TRAV and T

298 of 2C TCR-transgenic/RAG2(-/-) T cells into TCRalpha(-/-) vs ICAM(-/-)/TCRalpha(-/-) recipient anima

299 /-)), but not alphabeta cell-deficient mice (TCRalpha(-/-)), were more prone than wild-type mice to D

300 restricted clone that expresses the TRAV12-2 TCRalpha, which lacks residues previously shown to be cr