ライフサイエンスコーパス: L. major

1 L. major expresses two nucleobase permeases, NT3 that is

2 L. major infection enhanced N-Ras activity but inhibited

3 L. major infection is associated with self-limiting cuta

4 L. major MTHFR was expressed in yeast and recombinant en

5 L. major-exposed keratinocytes had no comparable effect.

6 recombinant murine interleukin-12 (rmIL-12), L. major SEAgs coadministered with both alum and rmIL-12

7 A L. major null mutant, Deltalmgat/Deltalmgat, was created

8 We have studied a L. major strain from a patient with nonhealing lesions t

9 compared to wild-type (WT) littermates after L. major infection.

10 tment of the first wave of neutrophils after L. major infection, a process that delays disease contro

11 led to mount an efficient Th1 response after L. major infection, produced more IL-4, and developed la

12 emination of parasites into the spleen after L. major infection.

13 transferred into mice at various times after L. major infection to determine the duration of presenta

14 vity of CTZ by factors of 110 and 58 against L. major and T. cruzi, with no appreciable toxicity to h

15 ls plays a critical role in immunity against L. major by controlling the migration of Th1 cells to th

16 ine receptor CXCR3 mediates immunity against L. major by recruiting IFN-gamma-producing T cells to th

17 the induction of protective immunity against L. major by regulating IL-12p70 production and migration

18 CD8(+) T cells in mediating immunity against L. major by transferring T cells from wild-type (WT) and

19 to become Th1 cells and protect mice against L. major following adoptive transfer into STAT1-sufficie

20 development of Th1 cells protective against L. major and instead stress the importance of STAT1 sign

21 tion of a protective T cell response against L. major infections.

22 ce were immunized with L. major SEAgs alone, L. major SEAgs coadministered with either alum (aluminum

23 d with liposomal amphotericin B (LAmB) in an L. major mouse model and analyzed the therapeutic effica

24 racterized the expression and function of an L. major phosphatase, which we termed LmPRL-1.

25 administered with both alum and rmIL-12, and L. major SEAgs coadministered with Montanide ISA 720.

26 ng lymph node cells from L. amazonensis- and L. major-infected mice at 10 weeks postinfection showed

27 oinoculated with trimannose-coated beads and L. major Trimannose treatment of L. major-infected mice

28 r alone, coinoculated with carrier beads and L. major, or coinoculated with trimannose-coated beads a

29 ctural differences between the T. brucei and L. major enzymes.

30 Comparisons of T. brucei with T. cruzi and L. major indicate a high degree of conservation among th

31 observed that Leishmania-infected humans and L. major-infected C57BL/6 mice exhibited substantial amo

32 These data suggest that L. infantum and L. major differentially activate keratinocytes to releas

33 proliferating in response to L. mexicana and L. major.

34 L. tarentolae and L. major genome annotation was transferred and these gen

35 plete resolution of chronic lesion in arg(-) L. major-infected mice.

36 hese results show that infection with arg(-) L. major results in chronic disease due in part to PD-1-

37 ce infected with arginase-deficient (arg(-)) L. major failed to completely resolve their lesion and m

38 However, as L. major infection typically progress over weeks to mont

39 sion and RNA processing events that occur as L. major transforms from non-infective procyclic promast

40 e killing of intracellular pathogens such as L. major, or a type 2 response, leading to antibody prod

41 tive against intracellular pathogens such as L. major.

42 teomic and immunoblot analyses of attenuated L. major strains deficient for LACK, the Leishmania orth

43 udy, we report development of two attenuated L. major strains-5ASKH-HP and LV39-HP-by continuous cult

44 Both virulent and avirulent L. major strains grew comparably in culture, but the avi

45 DC with caffeic acid phenethyl ester blocks L. major-induced IRF-1 and IRF-8 activation and IL-12 ex

46 ng differentiation of virulent forms in both L. major and L. amazonensis Our results also uncover a u

47 may shed light on the mechanisms employed by L. major to survive in the absence of LPG2-dependent gly

48 of T-bet did not prevent IL7R expression by L. major-responding CD4(+) T cells, nor did the absence

49 These findings showed that IDO induced by L. major infection attenuated innate and adaptive immune

50 Here, we report that DC priming by L. major infection results in the early activation of NF

51 uggest that proteins secreted or released by L. major in infected DC are a major source of peptides f

52 glf-1 mutants rescued by L. major glf, which behave as glf-1 hypomorphs, display

53 Furthermore, TLR2 triggering by L. major phosphoglycans is critical for neutrophil recru

54 cate a novel immune escape mechanism used by L. major parasites in the absence of IL-4/IL-13 signalin

55 Second, a reduced number of LCs carried L. major from the skin to the draining lymph nodes in Cc

56 secrete the extracellular portion of CD40L (L. major CD40LE).

57 ajor protected BALB/c mice against challenge L. major infection; the protection was accompanied by lo

58 or cells can express the IL7R during chronic L. major infection, which provides a potential means for

59 Distinct from chronic L. major infection, IL-10 blockade alone had no effect o

60 to produce sufficient amounts of NO to clear L. major.

61 Without CPCT, L. major parasites cannot incorporate choline into PC, y

62 rol and heightened mortality after T. cruzi, L. major, and Toxoplasma gondii infection, despite an ap

63 nerate null TOR1 or TOR2 mutants in cultured L. major promastigotes.

64 B6.WT mice over the first 2 wk of cutaneous L. major infection.

65 fection site and were resistant to cutaneous L. major infection.

66 ession of LmCOX subunit IV in LACK-deficient L. major restored thermotolerance and macrophage infecti

67 unction were also impaired in LACK-deficient L. major under these conditions.

68 hmania species that cause cutaneous disease, L. major and L. amazonensis, are poorly understood.

69 the IL7R on CD4(+) T cells activated during L. major infection.

70 fferentiation of protective Th1 cells during L. major infection, IFN-gammaR and STAT1 are dispensable

71 velopment of inappropriate Th17 cells during L. major infection.

72 not required for Th1 differentiation during L. major infection.

73 ry CD4(+) T cell population generated during L. major infection is capable of developing into either

74 nd lesions of BALB/c and C57BL/6 mice during L. major infection.

75 the specific IL-12 induction observed during L. major infection remains to be thoroughly elucidated.

76 dermis at steady-state conditions or during L. major infection express the alpha(E) chain (CD103) of

77 ) mice fail to develop a Th1 response during L. major infection.

78 ution of local inflammatory responses during L. major infection.

79 These results suggest that during L. major infection Ag-experienced T cells, rather than n

80 ell genes and pathways associated with early L. major infection in human myeloid-derived DCs.

81 described here using a CRISPR genome edited L. major strain (LmCen(-/-)).

82 nt with anti-IL-10R mAb virtually eliminated L. major parasites in both footpad and dermal infection

83 iasis in a mouse model, while also enhancing L. major specific T-cell immune responses in the infecte

84 doptive transfer of WT CD4(+) T cells or few L. major primed WT T(FH) cells reconstituted GC formatio

85 administration during the priming with fixed L. major protected BALB/c mice against challenge L. majo

86 he early generation of T(CM) cells following L. major infection indicates that T(CM) cells may not on

87 a deficit in lymph node expansion following L. major infection, as well as increased susceptibility.

88 e show that lymph node hypertrophy following L. major infection in mice is associated with increased

89 molecules and IL-12p40 production following L. major infection and were more efficient at inducing t

90 ction site at different timepoints following L. major infection.

91 l)phenyl)cinnolin-4-amine (NEU-1017, 68) for L. major and P. falciparum.

92 mice, revealing that PKR is dispensable for L. major growth in macrophages.

93 s establish a requirement for GDP-fucose for L. major viability and predict the existence of an essen

94 Similar to what was reported for L. major, APX depletion in L. amazonensis enhanced diffe

95 ibility to L. mexicana infection, unlike for L. major infection.

96 Restimulated lymph node cells from L. major-infected BALB/c-CXCR3(Tg) mice produced more in

97 5% of the IFN-gamma produced by T cells from L. major-infected mice under identical conditions.

98 Furthermore, T cells from L. major-susceptible BALB/c but not L. major-resistant C

99 d recombinant RNA editing exonuclease I from L. major, and recombinant RNA editing RNA ligase 1 from

100 monstrate that IRF-1 and IRF-8 obtained from L. major-infected human DC specifically bind to their co

101 NAD(P)H cytochrome b(5) oxidoreductase from L. major (LmNcb5or) knock-out mutants by targeted gene r

102 served that ectopic expression of LmPRL-1 in L. major led to an increased number of parasites in macr

103 of IL-10 that disrupts IFN-gamma activity in L. major-susceptible BALB/c mice.

104 sites within polycistronic gene clusters in L. major leads to read through transcription and increas

105 ntigens to specific cellular compartments in L. major and suggest that proteins secreted or released

106 CMV led to significantly enhanced disease in L. major-infected animals.

107 One allele of LmAQP1 was disrupted in L. major, and the resulting cells became 10-fold more re

108 Truncated OVA was expressed in L. major as part of a secreted or nonsecreted chimeric p

109 indicating TLR2-regulated Ras expression in L. major infection.

110 Corroborating these findings, in L. major-infected macrophages, CD40-induced SHP-1 phosph

111 on profile for several IFN response genes in L. major versus L. donovani DC infections.

112 I-PLCp caused a deficiency of protein-GPI in L. major, whereas glycosomal GPI-PLCp failed to produce

113 capability in T. brucei and the greatest in L. major.

114 Reduction of J in L. major resulted in genome-wide defects in transcriptio

115 h a requirement for 10-CHO-THF metabolism in L. major, and provide genetic and pharmacological valida

116 TLR2-TLR6 ligand) reduced L. major number in L. major-infected macrophages, accompanied by increased

117 , suggesting a potential role for CpG ODN in L. major treatment.

118 e response and subsequent disease outcome in L. major-infected mice.

119 ot attached to macromolecules are present in L. major as intermediates of protein-GPI and polysacchar

120 njugates had not been reported previously in L. major, but unexpectedly, we were unable to generate f

121 shows homology to another editing protein in L. major, which lacks the EEP motif (LmREX2*).

122 of homologs of the 9-1-1 complex subunits in L. major and found that LmRad9 and LmRad1 associate with

123 Tests in L. major using dd fusions to a panel of reporters and ce

124 An analysis of genomic UTRs in L. major showed that (i) the consensus APR is N(-3)N(-2)

125 d) and peptidoglycan (TLR2 ligand) increased L. major infection but reduced TLR9 expression, whereas

126 nistration reduced, but TLR6-shRNA increased L. major infection in BALB/c mice.

127 ion, Bim-/- mice had significantly increased L. major-specific CD4+ T-cell responses and were resista

128 short hairpin RNA enhanced the CD40-induced L. major parasite killing in susceptible BALB/c mice.

129 s from Leishmania braziliensis, L. infantum, L. major, L. tarentolae, Trypanosoma brucei and T. cruzi

130 sed to probe trafficking of GPI pools inside L. major.

131 esions, and these monocytes efficiently kill L. major parasites.

132 ajor infection, vaccination with heat-killed L. major plus CpG and SB203580 elicited complete protect

133 against infection compared with heat-killed L. major plus CpG without SB203580.

134 rotection conferred by vaccination with live L. major organisms in C57BL/6 mice.

135 may also improve the potential of the lpg2- L. major line to serve as a live parasite vaccine by ove

136 , we show that a strain of Leishmania major (L. major Seidman [LmSd]) that produces nonhealing cutane

137 h resistance to developing Leishmania major (L. major) infection.

138 ifferential expression data for L. mexicana, L. major and Leptomonas seymouri, we have identified sev

139 nd effector CD4 T-cell formation in mif(-/-) L. major-infected mice when compared to mice infected wi

140 lyses revealed a reduced ability of mif(-/-) L. major to activate antigen-presenting cells, resulting

141 hat developed during infection with mif(-/-) L. major demonstrated statistically significant differen

142 Mice infected with mif(-/-) L. major, when compared to the wild-type strain, also sh

143 lls from L. major-susceptible BALB/c but not L. major-resistant C57BL/6 mice fail to efficiently upre

144 (2)O(2) Earlier studies showed that APX-null L. major parasites are viable, accumulate higher levels

145 , we tested the infectivity of a new PG-null L. major mutant, which is inactivated in the two UDP-gal

146 The ability of L. major transgenic parasites to activate OT-I CD8(+) T

147 Analysis of L. major-infected BALB/c and IL-4Ralpha(-/-) inflammator

148 d as partially protective, in the context of L. major transmission by L. longipalpis sand flies.

149 ficant effect was detected in the context of L. major transmission by P. duboscqi, this DNA vaccine w

150 DM-sufficient APC, may change the course of L. major infection in the susceptible BALB/c mice.

151 thus offer a route to the rational design of L. major-specific GLO1 inhibitors.

152 merase chain reaction tests for detection of L. major.

153 TAT1 in preventing systemic dissemination of L. major infection.

154 d predominantly in the insect vector form of L. major, and immunofluorescence demonstrated that LmPOT

155 we used sand fly-derived metacyclic forms of L. major and preexposed the injection site to the bites

156 more potent linear competitive inhibitor of L. major than human GLO1 (Kis of 0.54 microM and 12.6 mi

157 Injection of L. major-activated dendritic cells promoted lymph node h

158 l animals at 2 wk post-needle inoculation of L. major, and this correlated with a 100-fold reduction

159 cessfully resolve infection by an isolate of L. major, despite a strong IFN-gamma response by the hos

160 responses that contribute to the killing of L. major.

161 against leishmanolysin-knock out mutants of L. major.

162 with a significant increase in the number of L. major-specific IFN-gamma-producing CD4+ T cells and a

163 and TNF-alpha in determining the outcome of L. major infection beyond a balance between Th1- and Th2

164 CR3 on T cells did not impact the outcome of L. major infection in C57BL/6 mice, which mounted a pred

165 mechanisms resulting in the fatal outcome of L. major infection in this gene-deficient mouse strain,

166 Fifty percent of L. major-knockout lines for the ecotin-like serine pepti

167 ishmaniasis and for long-term persistence of L. major.

168 mutant did not recapitulate the phenotype of L. major lpg2(-), instead resembling the L. major lipoph

169 We have analyzed the potential of L. major transgenic parasites, expressing the model anti

170 In cutaneous leishmaniasis, the protein of L. major, named inhibitor of serine peptidases (ISP) 2,

171 We found that resolution of L. major infection in C57BL/6 mice was associated with a

172 , in macrophages impaired the restriction of L. major replication in C57BL/6, but did not affect para

173 nt Leishmania species, a cutaneous strain of L. major and a visceral strain of Leishmania infantum, e

174 ere removed to produce an mif(-/-) strain of L. major This mutant strain replicated normally in vitro

175 The crystal structure of L. major GLO1 reveals differences in active site archite

176 When the substrain of L. major, LV39, was infected, lack of galectin-3 impaire

177 d beads and L. major Trimannose treatment of L. major-infected mice decreased the parasite load and s

178 rden, NO production, or host cell tropism of L. major during the acute or persistent phase of infecti

179 hat Lu. longipalpis is a competent vector of L. major parasites, being able to acquire parasites from

180 rovide a substantially more detailed view of L. major biology that will inform the field and potentia

181 In a high-content imaging assay on L. major-infected intraperitoneal mice macrophages, comp

182 te the pleiotropic effects that IL-27 has on L. major-driven Th1, Th2, and Th17 development, and rein

183 following stimulation with LPS/IFN-gamma or L. major.

184 , neutrophil migration, induced by the other L. major substrain, Friedlin, was unaffected, and the in

185 ozoa Leishmania major produces a peroxidase (L. major peroxidase; LmP) that exhibits activities chara

186 In response, L. major produces a peroxidase, L. major peroxidase (LmP), that helps to protect the par

187 r in Bim-/- and wild-type mice after primary L. major infection.

188 n-presenting cell requirement during primary L. major infection using a mouse model in which MHC II,

189 stingly, despite their resistance to primary L. major infection, Bim-/- mice displayed significantly

190 ralization of IL-18 in these animals reduced L. major titers and footpad swelling.

191 ce primed with these macrophages had reduced L. major infection, accompanied by higher IFN-gamma but

192 teine (BPPcysMPEG; TLR2-TLR6 ligand) reduced L. major number in L. major-infected macrophages, accomp

193 Both the cell-permeable peptides reduced L. major infection in BALB/c mice but not in CD40-defici

194 Whereas N-Ras silencing reduced L. major infection, K-Ras and H-Ras silencing enhanced t

195 iously, we characterized two closely related L. major genes (FKP40 and AFKP80) encoding bifunctional

196 In response, L. major produces a peroxidase, L. major peroxidase (LmP

197 nals failed to disrupt the early restrictive L. major infection site, which suggests that L. major do

198 f infection-induced immunity after secondary L. major challenge.

199 ilure to induce protection against secondary L. major challenge.

200 rm immunity, and were resistant to secondary L. major challenge, treated CD40L KO reactivated their l

201 1B, whereas keratinocytes exposed to several L. major isolates did not.

202 ages in vivo compared with a healing strain (L. major Friedlin V1).

203 In kinetic studies L. major and human enzymes were active with methylglyoxa

204 ture of LmP in a complex with its substrate, L. major cytochrome c (LmCytc) to 1.84 A, and compared t

205 is >4000-fold more active against human than L. major GLO1 (Kis of 0.13 microM and >500 microM respec

206 serine; these studies also established that L. major promastigotes require serine for optimal growth

207 es on the IL-12p35 promoter, indicating that L. major infection either directly stimulates a signalin

208 We observed that L. major enhanced N-Ras and H-Ras expression but inhibit

209 Our data revealed that L. major, but not L. donovani, induces expression of IRF

210 These data show that L. major infection induces macrophage VEGF-A production

211 These data show that L. major infection initiates enhanced vascular endotheli

212 L. major infection site, which suggests that L. major dominantly modifies the local milieu.

213 lished biological observations suggests that L. major has a relatively slow growth rate and can repli

214 As the L. major TyrRS pseudo-dimer is inherently asymmetric, co

215 -dependent metabolite is responsible for the L. major amastigote virulence defect, although further s

216 revealed the four subunits of the GCC in the L. major genome, and the role of the GCC in parasite met

217 ining revealed 12 candidate NST genes in the L. major genome, including LPG2 as well as a candidate e

218 lack of general transcription factors in the L. major, Trypanosoma brucei, and Trypanosoma cruzi (Tri

219 IL-12p40 during DC infection, indicating the L. major-induced expression of IL-12p40 is dependent upo

220 Correspondingly, null mutants of the L. major GDP-mannose transporter LPG2 lack PGs and are s

221 roxyacetone phosphate acyltransferase of the L. major localized in the peroxisome, important for grow

222 The biochemical characterization of the L. major phosphatase revealed that the enzyme is redox s

223 te plausibly irreversible attenuation of the L. major strain and its potential use as a vaccine strai

224 an epitope in the amino-terminal end of the L. major surface gp63 zinc metalloproteinase (leishmanol

225 of L. major lpg2(-), instead resembling the L. major lipophosphoglycan-deficient lpg1(-) mutant.

226 These data reveal the L. major-enhanced CD40-induced N-Ras activation as a nov

227 2 or anti-lipophosphoglycan Abs reversed the L. major-altered N-Ras and K-Ras expressions.

228 From these data, we conclude that the L. major phosphatase LmPRL-1 contributes to the intracel

229 MAX was also added to L. major-infected mouse peritoneal exudate cells (PECs),

230 In comparison to L. major controls, L. amazonensis-infected DCs secreted

231 on T cells in BALB/c mice may contribute to L. major susceptibility.

232 monstrate that this activity is essential to L. major promastigotes, the parasite forms found in the

233 sMPEG conferred antileishmanial functions to L. major-infected BALB/c-derived T cells in a macrophage

234 rmis, but only IL-4-producing cells homed to L. major-infected dermis.

235 Thus, immunity to L. major is mediated by at least two distinct population

236 ufficient to maintain protective immunity to L. major.

237 1 enhanced the susceptibility of the mice to L. major infection, and aggravated inflammatory response

238 s increases susceptibility of BALB/c mice to L. major.

239 Unc93b1(-/-) cells were highly permissive to L. major replication.

240 ction of the susceptible type 2 phenotype to L. major infection.

241 lopment of a TH1 response, and resistance to L. major infection in resistant C57BL/6 mice.

242 CXCR3 on T cells would enhance resistance to L. major infection in susceptible BALB/c mice.

243 scribed endosomal TLR-mediated resistance to L. major infection.

244 hagy contributes to macrophage resistance to L. major replication, and mechanistically explain the pr

245 dless of CD11b status, develop resistance to L. major.

246 knockout [KO]) mice were highly resistant to L. major infection, as evidenced by significantly (p < 0

247 T(CM) cells, CD62L(low) cells responding to L. major infection expressed the IL7R.

248 on, which are frequently seen in response to L. major infection.

249 s not bias the T helper cytokine response to L. major infection.

250 iled to participate in the GC in response to L. major or influenza virus infection.

251 ogenous IL-12 reversed the susceptibility to L. major infection in Ccr2(-/-) mice.

252 genes that underlie BALB/c susceptibility to L. major infections are poorly defined.

253 BALB/c mice are susceptible to L. major and show a nonprotective immunodominant CD4 T c

254 -9 (Tlr3/7/9(-/-)) are highly susceptible to L. major infection.

255 knockout (KO) mice are highly susceptible to L. major, treatment with rIL-12 during the first 2 wk of

256 n the present study, we developed transgenic L. major organisms which express and secrete the extrace

257 ffered no protection to subsequent wild-type L. major challenge, suggesting that the transgenic paras

258 a time when the lesion induced by wild-type L. major is completely resolved.

259 hen compared to mice infected with wild-type L. major Notably, effector CD4 T cells that developed du

260 major, yet inoculation with live, wild-type L. major remains the only successful vaccine in humans.

261 or newer epitopes not presented by wild-type L. major-infected APC.

262 es was similar to that elicited by wild-type L. major.

263 tamicin and paromomycin alone for ulcerative L. major disease.

264 , and 9, UNC93B1, or MyD88 failed to undergo L. major-induced autophagy.

265 ial for immunity against L. donovani, unlike L. major.

266 BALB/c mice were protected against virulent L. major challenge infection.

267 organisms protect BALB/c mice from virulent L. major challenge.

268 pg2- parasites were challenged with virulent L. major they were protected from disease.

269 itu hybridization was performed to visualize L. major parasites in fecal samples from the gorillas.

270 When L. major skin lesions of self-healing C57BL/6 mice reach

271 midine hemithioacetal is 40-fold better with L. major GLO1, whereas glutathione hemithioacetal is 300

272 Infection of mammalian cells with L. major modestly decreased IFNAR1 levels and attenuated

273 ination with GLA-SE following challenge with L. major by needle or infected sand fly bite in resistan

274 no visible lesions following challenge with L. major-infected sand flies, while non-immunized animal

275 y enhanced protection against challenge with L. major.

276 e in susceptible BALB/c mice challenged with L. major promastigotes was investigated.

277 ity responses in immune mice challenged with L. major, indicating that IL7R signaling contributes to

278 d interleukin-12p40 production compared with L. major infection of these same mice.

279 ion after 4 hours of infection compared with L. major infection, which correlated with promastigote t

280 Groups of BALB/c mice were immunized with L. major SEAgs alone, L. major SEAgs coadministered with

281 Mice immunized with L. major SEAgs had significantly smaller lesions that at

282 d or carrier (uncoated) beads, infected with L. major alone, coinoculated with carrier beads and L. m

283 ve CD4(+) Th1 immunity in mice infected with L. major and suggest that its neutralization may be a po

284 When MR(-/-) mice were infected with L. major and treated with trimannose beads, they did not

285 Mice infected with L. major exhibit similar changes depending upon disease

286 cells (DC) but not macrophages infected with L. major that secreted NT-OVA could prime OT-I T cells t

287 Here we found that macrophages infected with L. major undergo autophagy, which effectively accounted

288 f optimal Th1 immunity in mice infected with L. major.

289 mB-3 unexpectedly exacerbated infection with L. major (it increased the cutaneous lesion size and the

290 Infection with L. major LV39 but not Friedlin induced higher levels of

291 ine repertoire at the site of infection with L. major was driven, in part, by pathogen-induced CCL7.

292 UNC93B1 mutant phenotype upon infection with L. major.

293 lymph node, develop a chronic infection with L. major.

294 ions following an intradermal infection with L. major.

295 ent in DM are protected from infections with L. major.

296 , type 1 cytokines than mice inoculated with L. major alone within the first 48 h of infection.

297 d that challenging dysbiotic naive mice with L. major or testing for contact hypersensitivity results

298 ctive immunity, we infected Bim-/- mice with L. major.

299 romoter, and then examined the outcomes with L. major infection.

300 ssed N-Ras short hairpin RNA and pulsed with L. major-expressed MAPK10 enhanced MAPK10-specific Th1-t

301 First, unlike wild-type (WT) L. major, iscl(-) mutants do not trigger polarized T cel