Comprehensive Analysis of CD4+ T Cell Responses to CMV pp65 Antigen Restricted by Single HLA-DR, -DQ, and -DP Allotype Within an Individual
Within an individual, six different HLA class II heterodimers are expressed co-dominantly by two alleles of HLA-DR, -DQ, and -DP loci. However, it remained unclear which HLA allotypes were used in T cell responses to a given antigen. For the measurement of the CD4+ T cell responses restricted by a s...
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Frontiers Media S.A.
2021-02-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2020.602014/full |
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| author | You-Seok Hyun You-Seok Hyun Hyeong-A Jo Hyeong-A Jo Yong-Hun Lee Yong-Hun Lee Sun-Mi Kim In-Cheol Baek Hyun-Jung Sohn Hyun-Il Cho Tai-Gyu Kim Tai-Gyu Kim Tai-Gyu Kim |
| author_facet | You-Seok Hyun You-Seok Hyun Hyeong-A Jo Hyeong-A Jo Yong-Hun Lee Yong-Hun Lee Sun-Mi Kim In-Cheol Baek Hyun-Jung Sohn Hyun-Il Cho Tai-Gyu Kim Tai-Gyu Kim Tai-Gyu Kim |
| author_sort | You-Seok Hyun |
| collection | DOAJ |
| description | Within an individual, six different HLA class II heterodimers are expressed co-dominantly by two alleles of HLA-DR, -DQ, and -DP loci. However, it remained unclear which HLA allotypes were used in T cell responses to a given antigen. For the measurement of the CD4+ T cell responses restricted by a single HLA allotype, we established a panel of artificial antigen-presenting cells (aAPCs) expressing each single HLA allele of 20 HLA-DRB1, 16 HLA-DQ, and 13 HLA-DP alleles. CD4+ T cell responses to cytomegalovirus (CMV) pp65 restricted by single HLA class II allotype defined in 45 healthy donors. The average magnitude of CD4+ T cell responses by HLA-DR allotypes was higher than HLA-DQ and HLA-DP allotypes. CD4+ T cell responses by DRA*01:01/DRB1*04:06, DQA1*01:02/DQB1*06:02, DPA1*02:02/DPB1*05:01 were higher among the other alleles in each HLA-DR, -DQ, and -DP locus. Interestingly, the frequencies of HLA-DR alleles and the positivity of specific allotypes showed an inverse correlation. One allotype within individuals is dominantly used in CD4+ T cell response in 49% of donors, and two allotypes showed that in 7% of donors, and any positive response was detected in 44% of donors. Even if one individual had several dominant alleles, CD4+ T cell responses tended to be restricted by only one of them. Furthermore, CD8+ and CD4+ T cell responses by HLA class I and class II were correlated. Our results demonstrate that the CD4+ T cell preferentially use a few dominant HLA class II allotypes within individuals, similar to CD8+ T cell response to CMV pp65. |
| first_indexed | 2024-12-17T07:20:33Z |
| format | Article |
| id | doaj.art-b77c87918d06494baf7d74c6b1e71c1e |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-17T07:20:33Z |
| publishDate | 2021-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-b77c87918d06494baf7d74c6b1e71c1e2022-12-21T21:58:47ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-02-011110.3389/fimmu.2020.602014602014Comprehensive Analysis of CD4+ T Cell Responses to CMV pp65 Antigen Restricted by Single HLA-DR, -DQ, and -DP Allotype Within an IndividualYou-Seok Hyun0You-Seok Hyun1Hyeong-A Jo2Hyeong-A Jo3Yong-Hun Lee4Yong-Hun Lee5Sun-Mi Kim6In-Cheol Baek7Hyun-Jung Sohn8Hyun-Il Cho9Tai-Gyu Kim10Tai-Gyu Kim11Tai-Gyu Kim12Department of Microbiology, College of Medicine, The Catholic University of Korea, Seoul, South KoreaDepartment of Biomedicine and Health Sciences, College of Medicine, The Catholic University of Korea, Seoul, South KoreaDepartment of Microbiology, College of Medicine, The Catholic University of Korea, Seoul, South KoreaDepartment of Biomedicine and Health Sciences, College of Medicine, The Catholic University of Korea, Seoul, South KoreaDepartment of Microbiology, College of Medicine, The Catholic University of Korea, Seoul, South KoreaDepartment of Biomedicine and Health Sciences, College of Medicine, The Catholic University of Korea, Seoul, South KoreaCatholic Hematopoietic Stem Cell Bank, College of Medicine, The Catholic University of Korea, Seoul, South KoreaCatholic Hematopoietic Stem Cell Bank, College of Medicine, The Catholic University of Korea, Seoul, South KoreaTranslational and Clinical Division, ViGenCell Inc., Seoul, South KoreaTranslational and Clinical Division, ViGenCell Inc., Seoul, South KoreaDepartment of Microbiology, College of Medicine, The Catholic University of Korea, Seoul, South KoreaDepartment of Biomedicine and Health Sciences, College of Medicine, The Catholic University of Korea, Seoul, South KoreaCatholic Hematopoietic Stem Cell Bank, College of Medicine, The Catholic University of Korea, Seoul, South KoreaWithin an individual, six different HLA class II heterodimers are expressed co-dominantly by two alleles of HLA-DR, -DQ, and -DP loci. However, it remained unclear which HLA allotypes were used in T cell responses to a given antigen. For the measurement of the CD4+ T cell responses restricted by a single HLA allotype, we established a panel of artificial antigen-presenting cells (aAPCs) expressing each single HLA allele of 20 HLA-DRB1, 16 HLA-DQ, and 13 HLA-DP alleles. CD4+ T cell responses to cytomegalovirus (CMV) pp65 restricted by single HLA class II allotype defined in 45 healthy donors. The average magnitude of CD4+ T cell responses by HLA-DR allotypes was higher than HLA-DQ and HLA-DP allotypes. CD4+ T cell responses by DRA*01:01/DRB1*04:06, DQA1*01:02/DQB1*06:02, DPA1*02:02/DPB1*05:01 were higher among the other alleles in each HLA-DR, -DQ, and -DP locus. Interestingly, the frequencies of HLA-DR alleles and the positivity of specific allotypes showed an inverse correlation. One allotype within individuals is dominantly used in CD4+ T cell response in 49% of donors, and two allotypes showed that in 7% of donors, and any positive response was detected in 44% of donors. Even if one individual had several dominant alleles, CD4+ T cell responses tended to be restricted by only one of them. Furthermore, CD8+ and CD4+ T cell responses by HLA class I and class II were correlated. Our results demonstrate that the CD4+ T cell preferentially use a few dominant HLA class II allotypes within individuals, similar to CD8+ T cell response to CMV pp65.https://www.frontiersin.org/articles/10.3389/fimmu.2020.602014/fullHLA-DRHLA-DQHLA-DPMHC class II allelesCD4+ T cellscytomegalovirus pp65 antigen |
| spellingShingle | You-Seok Hyun You-Seok Hyun Hyeong-A Jo Hyeong-A Jo Yong-Hun Lee Yong-Hun Lee Sun-Mi Kim In-Cheol Baek Hyun-Jung Sohn Hyun-Il Cho Tai-Gyu Kim Tai-Gyu Kim Tai-Gyu Kim Comprehensive Analysis of CD4+ T Cell Responses to CMV pp65 Antigen Restricted by Single HLA-DR, -DQ, and -DP Allotype Within an Individual Frontiers in Immunology HLA-DR HLA-DQ HLA-DP MHC class II alleles CD4+ T cells cytomegalovirus pp65 antigen |
| title | Comprehensive Analysis of CD4+ T Cell Responses to CMV pp65 Antigen Restricted by Single HLA-DR, -DQ, and -DP Allotype Within an Individual |
| title_full | Comprehensive Analysis of CD4+ T Cell Responses to CMV pp65 Antigen Restricted by Single HLA-DR, -DQ, and -DP Allotype Within an Individual |
| title_fullStr | Comprehensive Analysis of CD4+ T Cell Responses to CMV pp65 Antigen Restricted by Single HLA-DR, -DQ, and -DP Allotype Within an Individual |
| title_full_unstemmed | Comprehensive Analysis of CD4+ T Cell Responses to CMV pp65 Antigen Restricted by Single HLA-DR, -DQ, and -DP Allotype Within an Individual |
| title_short | Comprehensive Analysis of CD4+ T Cell Responses to CMV pp65 Antigen Restricted by Single HLA-DR, -DQ, and -DP Allotype Within an Individual |
| title_sort | comprehensive analysis of cd4 t cell responses to cmv pp65 antigen restricted by single hla dr dq and dp allotype within an individual |
| topic | HLA-DR HLA-DQ HLA-DP MHC class II alleles CD4+ T cells cytomegalovirus pp65 antigen |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2020.602014/full |
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