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Mycobacterium tuberculosis peptide E7/HLA-DRB1 tetramers with different HLA-DR alleles bound CD4⁺ T cells might share identical CDR3 region.

ABSTRACT: Human CD4⁺ T cells play an important role in the immune response to Mycobacterium tuberculosis (MTB). However, little is known about the spectratyping characteristics of the CD4⁺ T-cell receptor (TCR) ?- and ?-chains CDR3 region in tuberculosis (TB) patients. We sorted MTB peptide E7-bound CD4⁺ T cells by using E7/HLA-DR tetramers constructed with different HLA-DRB1 alleles and extracted the CDR3 amino-acid sequences of TCR ?- and ?-chains. The results showed that the CDR3 sequences of E7-bound CD4⁺ T cells were completely or partially identical in a single patient. The sequences of MTB peptide C5-bound CD4⁺ T cells shared another, and non-peptide bound CD4⁺ T cells, as well as unbound CD4⁺ T cells with tetramers were different from each other. Specifically, diverse CDR3 sequences of E7-bound CD4⁺ T cells displayed similar protein tertiary structure in one TB patient. In summary, the TCR ?- and ?-chains of CDR3 lineage of CD4⁺ T cells in TB patients apparently drifted, and the predominant CDR3 sequences of TCR ?- and ?-chains that recognized the MTB antigen exhibited peptide specificity, and certain HLA-DR restriction was also established. This study elucidates the possible causes and mechanisms of peptide-specific CD4⁺ T-cell-related presentation against MTB.

SUBMITTER: Gan Y

PROVIDER: S-EPMC6028479 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Mycobacterium tuberculosis peptide E7/HLA-DRB1 tetramers with different HLA-DR alleles bound CD4+ T cells might share identical CDR3 region.

Gan Yichuan Y Wang Cong C Fang Yimin Y Yao Yanan Y Tu Xiaoxin X Wang Jiao J Huang Xi X Tan Yaoju Y Chen Tao T Zhang Kouxing K Shen Yanming Y Zhou Lin L Liu Jianxiong J Lai Xiaomin X

Scientific reports 20180702 1

Human CD4+ T cells play an important role in the immune response to Mycobacterium tuberculosis (MTB). However, little is known about the spectratyping characteristics of the CD4+ T-cell receptor (TCR) α- and β-chains CDR3 region in tuberculosis (TB) patients. We sorted MTB peptide E7-bound CD4+ T cells by using E7/HLA-DR tetramers constructed with different HLA-DRB1 alleles and extracted the CDR3 amino-acid sequences of TCR α- and β-chains. The results showed tha ...[more]

PMID: 29967390

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Project description:ObjectiveSevere fever with thrombocytopenia syndrome (SFTS) is an emerging hemorrhagic fever caused by a tick-borne bunyavirus (SFTSV) in East Asian countries. The role of human leukocyte antigen (HLA) in resistance and susceptibility to SFTSV is not known. We investigated the correlation of HLA locus A, B and DRB1 alleles with the occurrence of SFTS.MethodsA total of 84 confirmed SFTS patients (patient group) and 501 unrelated non-SFTS patients (healthy individuals as control group) from Shandong Province were genotyped by PCR-sequence specific oligonucleotide probe (PCR-SSOP) for HLA-A, B and DRB1 loci.Allele frequency was calculated and compared using χ2 test or the Fisher's exact test. A corrected P value was calculated with a bonferronis correction. Odds Ratio (OR) and 95% confidence intervals (CI) were calculated by Woolf's method.ResultsA total of 11 HLA-A, 23 HLA-B and 12 HLA-DRB1 alleles were identified in the patient group, whereas 15 HLA-A, 30 HLA-B and 13 HLA-DRB1 alleles were detected in the control group. The frequencies of A*30 and B*13 in the SFTS patient group were lower than that in the control group (P = 0.0341 and 0.0085, Pc = 0.5115 and 0.252). The ORs of A*30 and B*13 in the SFTS patient group were 0.54 and 0.49, respectively. The frequency of two-locus haplotype A*30-B*13 was lower in the patient group than in the control group(5.59% versus 12.27%, P = 0.037,OR = 0.41, 95%CI = 0.18-0.96) without significance(Pc>0.05). A*30-B*13-DRB1*07 and A*02-B*15-DRB1*04 had strong associations with SFTS resistance and susceptibility respectively (Pc = 0.0412 and 0.0001,OR = 0.43 and 5.07).ConclusionThe host HLA class I polymorphism might play an important role with the occurrence of SFTS. Negative associations were observed with HLA-A*30, HLA-B*13 and Haplotype A*30-B*13, although the associations were not statistically significant. A*30-B*13-DRB1*07 had negative correlation with the occurrence of SFTS; in contrast, haplotype A*02-B*15-DRB1*04 was positively correlated with SFTS.

Dataset Information

Mycobacterium tuberculosis peptide E7/HLA-DRB1 tetramers with different HLA-DR alleles bound CD4⁺ T cells might share identical CDR3 region.

Publications

Mycobacterium tuberculosis peptide E7/HLA-DRB1 tetramers with different HLA-DR alleles bound CD4<sup>+</sup> T cells might share identical CDR3 region.

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