Germline IgM predicts T cell immunity to Pneumocystis
Pneumocystis is the most common fungal pulmonary infection in children under the age of 5 years. In children with primary immunodeficiency, Pneumocystis often presents at 3–6 months of age, a time period that coincides with the nadir of maternal IgG and when IgM is the dominant Ig isotype. Because B...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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American Society for Clinical investigation
2022-09-01
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| Series: | JCI Insight |
| Subjects: | |
| Online Access: | https://doi.org/10.1172/jci.insight.161450 |
| _version_ | 1797634394750451712 |
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| author | Kristin Noell Guixiang Dai Dora Pungan Anna Ebacher Janet E. McCombs Samuel J. Landry Jay K. Kolls |
| author_facet | Kristin Noell Guixiang Dai Dora Pungan Anna Ebacher Janet E. McCombs Samuel J. Landry Jay K. Kolls |
| author_sort | Kristin Noell |
| collection | DOAJ |
| description | Pneumocystis is the most common fungal pulmonary infection in children under the age of 5 years. In children with primary immunodeficiency, Pneumocystis often presents at 3–6 months of age, a time period that coincides with the nadir of maternal IgG and when IgM is the dominant Ig isotype. Because B cells are the dominant antigen-presenting cells for Pneumocystis, we hypothesized the presence of fungal-specific IgMs in humans and mice and that these IgM specificities would predict T cell antigens. We detected fungal-specific IgMs in human and mouse sera and utilized immunoprecipitation to determine whether any antigens were similar across donors. We then assessed T cell responses to these antigens and found anti-Pneumocystis IgM in WT mice, Aicda–/– mice, and in human cord blood. Immunoprecipitation of Pneumocystis murina with human cord blood identified shared antigens among these donors. Using class II MHC binding prediction, we designed peptides with these antigens and identified robust peptide-specific lung T cell responses after P. murina infection. After mice were immunized with 2 of the antigens, adoptive transfer of vaccine-elicited CD4+ T cells showed effector activity, suggesting that these antigens contain protective Pneumocystis epitopes. These data support the notion that germline-encoded IgM B cell receptors are critical in antigen presentation and T cell priming in early Pneumocystis infection. |
| first_indexed | 2024-03-11T12:08:13Z |
| format | Article |
| id | doaj.art-dabb1d72bf4a42cca8fd8aeb0b069a44 |
| institution | Directory Open Access Journal |
| issn | 2379-3708 |
| language | English |
| last_indexed | 2024-03-11T12:08:13Z |
| publishDate | 2022-09-01 |
| publisher | American Society for Clinical investigation |
| record_format | Article |
| series | JCI Insight |
| spelling | doaj.art-dabb1d72bf4a42cca8fd8aeb0b069a442023-11-07T16:24:31ZengAmerican Society for Clinical investigationJCI Insight2379-37082022-09-01717Germline IgM predicts T cell immunity to PneumocystisKristin NoellGuixiang DaiDora PunganAnna EbacherJanet E. McCombsSamuel J. LandryJay K. KollsPneumocystis is the most common fungal pulmonary infection in children under the age of 5 years. In children with primary immunodeficiency, Pneumocystis often presents at 3–6 months of age, a time period that coincides with the nadir of maternal IgG and when IgM is the dominant Ig isotype. Because B cells are the dominant antigen-presenting cells for Pneumocystis, we hypothesized the presence of fungal-specific IgMs in humans and mice and that these IgM specificities would predict T cell antigens. We detected fungal-specific IgMs in human and mouse sera and utilized immunoprecipitation to determine whether any antigens were similar across donors. We then assessed T cell responses to these antigens and found anti-Pneumocystis IgM in WT mice, Aicda–/– mice, and in human cord blood. Immunoprecipitation of Pneumocystis murina with human cord blood identified shared antigens among these donors. Using class II MHC binding prediction, we designed peptides with these antigens and identified robust peptide-specific lung T cell responses after P. murina infection. After mice were immunized with 2 of the antigens, adoptive transfer of vaccine-elicited CD4+ T cells showed effector activity, suggesting that these antigens contain protective Pneumocystis epitopes. These data support the notion that germline-encoded IgM B cell receptors are critical in antigen presentation and T cell priming in early Pneumocystis infection.https://doi.org/10.1172/jci.insight.161450ImmunologyInfectious disease |
| spellingShingle | Kristin Noell Guixiang Dai Dora Pungan Anna Ebacher Janet E. McCombs Samuel J. Landry Jay K. Kolls Germline IgM predicts T cell immunity to Pneumocystis JCI Insight Immunology Infectious disease |
| title | Germline IgM predicts T cell immunity to Pneumocystis |
| title_full | Germline IgM predicts T cell immunity to Pneumocystis |
| title_fullStr | Germline IgM predicts T cell immunity to Pneumocystis |
| title_full_unstemmed | Germline IgM predicts T cell immunity to Pneumocystis |
| title_short | Germline IgM predicts T cell immunity to Pneumocystis |
| title_sort | germline igm predicts t cell immunity to pneumocystis |
| topic | Immunology Infectious disease |
| url | https://doi.org/10.1172/jci.insight.161450 |
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