The H2-A Class II molecule α/β-chain cis-mismatch severely affects cell surface expression, selection of conventional CD4+ T cells and protection against TB infection
IntroductionTo dissect the role of the part of the H2 complex comprised of the MHC-II genes in the control of tuberculosis (TB) infection, we previously established a panel of recombinant congenic mouse strains bearing different segments of the H2j haplotype on the B6 (H2b) genetic background. Fine...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-06-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1183614/full |
| _version_ | 1797797726539218944 |
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| author | Nadezhda Logunova Marina Kapina Elena Kondratieva Alexander Apt |
| author_facet | Nadezhda Logunova Marina Kapina Elena Kondratieva Alexander Apt |
| author_sort | Nadezhda Logunova |
| collection | DOAJ |
| description | IntroductionTo dissect the role of the part of the H2 complex comprised of the MHC-II genes in the control of tuberculosis (TB) infection, we previously established a panel of recombinant congenic mouse strains bearing different segments of the H2j haplotype on the B6 (H2b) genetic background. Fine genetic mapping, gene sequencing and assessment of TB phenotypes resulted in identification of the H2-Ab gene as a major factor of TB control.MethodsWe further narrowed the MHC-II H2j interval by spotting a new recombination event, sequencing newly established DNA configuration and establishing a mouse strain B6.I-103 in which j/b recombination occurred within the coding sequence of the H2-Ab gene.ResultsUnexpectedly, a novel H2-Aαb/AβjE0 haplotype provided exclusively high susceptibility to TB challenge. Immunologic analysis revealed an altered CD4+ T-cell selection and maintenance in B6.I-103 mice, as well as seriously impaired expression of the H2-Aαb/Aβj molecule on the surface of antigen presenting cells. Unlike previously reported cases of Class II malfunctioning, the defective phenotype arose not from strong structural mutations, but from regular recombination events within the MHC-II recombination hot spot region.DiscussionOur findings provide evidence that Class II α/β-chain cis-allelic mismatches created by regular genetic recombination may severely affect immune system functioning. This issue is discussed in the context of the MHC evolution. |
| first_indexed | 2024-03-13T03:53:45Z |
| format | Article |
| id | doaj.art-4b8cb5caf561460795d7f9e14cc25016 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-13T03:53:45Z |
| publishDate | 2023-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-4b8cb5caf561460795d7f9e14cc250162023-06-22T09:10:49ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-06-011410.3389/fimmu.2023.11836141183614The H2-A Class II molecule α/β-chain cis-mismatch severely affects cell surface expression, selection of conventional CD4+ T cells and protection against TB infectionNadezhda LogunovaMarina KapinaElena KondratievaAlexander AptIntroductionTo dissect the role of the part of the H2 complex comprised of the MHC-II genes in the control of tuberculosis (TB) infection, we previously established a panel of recombinant congenic mouse strains bearing different segments of the H2j haplotype on the B6 (H2b) genetic background. Fine genetic mapping, gene sequencing and assessment of TB phenotypes resulted in identification of the H2-Ab gene as a major factor of TB control.MethodsWe further narrowed the MHC-II H2j interval by spotting a new recombination event, sequencing newly established DNA configuration and establishing a mouse strain B6.I-103 in which j/b recombination occurred within the coding sequence of the H2-Ab gene.ResultsUnexpectedly, a novel H2-Aαb/AβjE0 haplotype provided exclusively high susceptibility to TB challenge. Immunologic analysis revealed an altered CD4+ T-cell selection and maintenance in B6.I-103 mice, as well as seriously impaired expression of the H2-Aαb/Aβj molecule on the surface of antigen presenting cells. Unlike previously reported cases of Class II malfunctioning, the defective phenotype arose not from strong structural mutations, but from regular recombination events within the MHC-II recombination hot spot region.DiscussionOur findings provide evidence that Class II α/β-chain cis-allelic mismatches created by regular genetic recombination may severely affect immune system functioning. This issue is discussed in the context of the MHC evolution.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1183614/fullH2-recombinant miceMHC-IIrecombination hot spotT-cell selectionclass II expressiontuberculosis infection |
| spellingShingle | Nadezhda Logunova Marina Kapina Elena Kondratieva Alexander Apt The H2-A Class II molecule α/β-chain cis-mismatch severely affects cell surface expression, selection of conventional CD4+ T cells and protection against TB infection Frontiers in Immunology H2-recombinant mice MHC-II recombination hot spot T-cell selection class II expression tuberculosis infection |
| title | The H2-A Class II molecule α/β-chain cis-mismatch severely affects cell surface expression, selection of conventional CD4+ T cells and protection against TB infection |
| title_full | The H2-A Class II molecule α/β-chain cis-mismatch severely affects cell surface expression, selection of conventional CD4+ T cells and protection against TB infection |
| title_fullStr | The H2-A Class II molecule α/β-chain cis-mismatch severely affects cell surface expression, selection of conventional CD4+ T cells and protection against TB infection |
| title_full_unstemmed | The H2-A Class II molecule α/β-chain cis-mismatch severely affects cell surface expression, selection of conventional CD4+ T cells and protection against TB infection |
| title_short | The H2-A Class II molecule α/β-chain cis-mismatch severely affects cell surface expression, selection of conventional CD4+ T cells and protection against TB infection |
| title_sort | h2 a class ii molecule α β chain cis mismatch severely affects cell surface expression selection of conventional cd4 t cells and protection against tb infection |
| topic | H2-recombinant mice MHC-II recombination hot spot T-cell selection class II expression tuberculosis infection |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1183614/full |
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