人白细胞抗原 B(HLA-B)携带 Bw4对急性HIV-1感染者 Gag-特异性T 细胞应答的影响
Bw4 motif expressed on HLA-B antigen affects HIV-1 specific T cell responses induced in patients with acute HIV-1 infection
摘要目的:研究人白细胞抗原HLA-B携带Bw4是否对急性HIV-1感染者Gag-特异的T细胞应答产生影响。方法用HIV-1 CRF01_A/E Gag多肽刺激36例HIV-1感染者在急性感染6个月时的外周血单个核细胞( PBMCs),并用ELISPOT技术检测HIV-1特异性T细胞应答。用序列特异性引物-聚合酶链反应( SSP-PCR)技术检测HIV-1感染者HLA分型及HLA-B携带Bw4、Bw6的分型。结果(1)在36例急性HIV-1感染者中,18例HLA-B不携带Bw4的感染者病毒调定点是4.49±0.56,18例HLA-B携带Bw4的感染者病毒调定点是3.78±0.75,前者的病毒调定点高于后者( P=0.005)。(2)HLA-B不携带Bw4的急性HIV-1感染者中15例可对P24肽库产生应答,而HLA-B携带Bw4的急性HIV-1感染者只有11例可对P24肽库产生应答,但差异无统计学意义。 HLA-B不携带Bw4的急性HIV-1感染者P24-特异的T细胞应答强度是(1317.8±1238.0) SFC/106 PBMCs,强于HLA-B携带 Bw4的急性 HIV-1感染者 P24-特异的 T 细胞应答强度[(549.9±778.5) SFC/106 PBMCs],差异有统计学意义(P=0.032)。然而两组感染者诱导产生的P17、P15特异性T细胞应答强度相当。 HLA-B不携带Bw4的急性HIV-1感染者对28条P24单肽的应答宽度是2(0~5)条,大于HLA-B携带Bw4的急性HIV-1感染者,其应答宽度是1(0~4)条( P=0.080)。(3) HLA-B不携带Bw4的急性HIV-1感染者病毒载量与P24特异的T细胞应答强度呈负相关(rs=-0.482,P=0.043),且与P24单肽的应答宽度呈负相关(rs=-0.496,P=0.036)。然而HLA-B携带Bw4的急性HIV-1感染者P24特异的T细胞应答强度与病毒载量、CD4细胞计数均无关,而且P24单肽的应答宽度与病毒载量无关。结论与HLA-B不携带Bw4的急性HIV-1感染者比较,尽管HLA-B携带Bw4的急性HIV-1感染者病毒调定点低,但其产生的P24-特异性T细胞应答强度弱且对P24单肽的应答宽度窄。
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abstractsObjective To investigate whether Bw4 motif expressed on HLA-B affects Gag-specific T cell responses in patients with acute HIV-1 infection.Methods Sequence specific primer polymerase chain reaction ( SSP-PCR) was performed for human leukocyte antigen ( HLA) typing.Peripheral blood mononuclear cells ( PBMCs) from 36 patients with six months of acute HIV-1 infection were stimulated with HIV-1 CRF01_A/E Gag peptides to detect the HIV-1 specific T cell responses by using ELISPOT assay. Results (1) The set point viral load of 18 patients carrying no Bw4 motif on HLA-B was 4.49±0.56 which was higher than that in other 18 patients carrying 1-2 Bw4 motif(s) on HLA-B (3.78±0.75) (P=0.005). (2) T cells from 26 out of 36 patients with acute HIV-1 infection responded to P24 peptides pool including 15 patients carrying no Bw4 motif on HLA-B and 11 patients carrying 1-2 Bw4 motif( s) on HLA-B, but no significant difference was observed between them (P>0.05).The magnitude of P24-specific T cell responses induced in patients carrying no Bw4 motif on HLA-B was (1317.8 ±1238.0) SFC/106 PBMCs which was greater than that induced in patients carrying 1-2 Bw4 motif(s) on HLA-B [(549.9±778.5) SFC/106 PBMCs] ( P=0.032) .The breadth of T cell responses to P24 peptides was 2(0-5) in patients carrying no Bw4 motif on HLA-B which was broader than that of patients carrying 1-2 Bw4 motif(s) on HLA-B [1(0-4)] (P=0.080).(3) The viral loads of HIV-1 infected patients carrying no Bw4 motif on HLA-B were negatively correlated with the magnitude of P24-specific T cell responses (rs=-0.482, P=0.043) and the breadth of responses to P24 peptides (rs=-0.496, P=0.036).No correlations were observed between viral loads and the magnitude or breadth of P24-specific T cell responses in HIV-1 infected patients carrying 1-2 Bw4 motif(s) on HLA-B.Conclusion Compared with HIV-1 infected patients carrying no Bw4 motif on HLA-B, the patients carrying 1-2 Bw4 motif( s) on HLA-B showed lower levels of set point viral load, weak-ened magnitude of P24-specific T cell responses and narrowed breadth of responses to P24 peptides.
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