{"doi":"10.1189/jlb.0804482","title":"The CD4+ T cell immunodominant <i>Anaplasma marginale</i> major surface protein 2 stimulates γδ T cell clones that express unique T cell receptors","abstract":"<jats:title>Abstract</jats:title>\n               <jats:p>Major surface protein 2 (MSP2) of the bovine rickettsial pathogen Anaplasma marginale is an abundant, serologically immunodominant outer membrane protein. Immunodominance partially results from numerous CD4+ T cell epitopes in highly conserved amino and carboxy regions and the central hypervariable region of MSP2. However, in long-term cultures of lymphocytes stimulated with A. marginale, workshop cluster 1 (WC1)+ γδ T cells and CD4+ αβ T cells proliferated, leading to a predominance of γδ T cells. As γδ T cells proliferate in A. marginale-stimulated lymphocyte cultures, this study hypothesized that γδ T cells respond to the abundant, immunodominant MSP2. To test this hypothesis, γδ T cell clones were isolated from MSP2 vaccinates and assessed for antigen-specific proliferation and interferon-γ secretion. Seven WC1+ γδ T cell clones responded to A. marginale and MSP2, and three of these proliferated to overlapping peptides from the conserved carboxy region. The γδ T cell response was not major histocompatibility complex-restricted, although it required antigen-presenting cells and was blocked by addition of antibody specific for the T cell receptor (TCR). Sequence analysis of TCR-γ and -δ chains of peripheral blood lymphocytes identified two novel TCR-γ chain constant (Cγ) regions. It is important that all seven MSP2-specific γδ T cell clones used the same one of these novel Cγ regions. The TCR complementarity-determining region 3 was less conserved than those of MSP2-specific CD4+ αβ T cell clones. Together, these data indicate that WC1+ γδ T cells recognize A. marginale MSP2 through the TCR and contribute to the immunodominant response to this protein.</jats:p>","journal":"Journal of Leukocyte Biology","year":2004,"id":628794,"datarank":0.6090664515819629,"base_score":4.060443010546419,"endowment":4.060443010546419,"self_citation_contribution":0.6090664515819629,"citation_network_contribution":0.0,"self_endowment_contribution":0.6090664515819629,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":57,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1535813,"name":"Junzo Norimine","orcid":null,"position":1,"is_corresponding":false},{"id":1628208,"name":"Mitchell S Abrahamsen","orcid":null,"position":2,"is_corresponding":false},{"id":1628209,"name":"Guy H Palmer","orcid":null,"position":3,"is_corresponding":false},{"id":1628210,"name":"Wendy C Brown","orcid":null,"position":4,"is_corresponding":false},{"id":1628206,"name":"Kevin K Lahmers","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"The CD4+ T cell immunodominant <i>Anaplasma marginale</i> major surface protein 2 stimulates γδ T cell clones that express unique T cell receptors","abstract":"Major surface protein 2 (MSP2) of the bovine rickettsial pathogen Anaplasma marginale is an abundant, serologically immunodominant outer membrane protein. Immunodominance partially results from numerous CD4+ T cell epitopes in highly conserved amino and carboxy regions and the central hypervariable region of MSP2. However, in long-term cultures of lymphocytes stimulated with A. marginale, workshop cluster 1 (WC1)+ gammadelta T cells and CD4+ alphabeta T cells proliferated, leading to a predominance of gammadelta T cells. As gammadelta T cells proliferate in A. marginale-stimulated lymphocyte cultures, this study hypothesized that gammadelta T cells respond to the abundant, immunodominant MSP2. To test this hypothesis, gammadelta T cell clones were isolated from MSP2 vaccinates and assessed for antigen-specific proliferation and interferon-gamma secretion. Seven WC1+ gammadelta T cell clones responded to A. marginale and MSP2, and three of these proliferated to overlapping peptides from the conserved carboxy region. The gammadelta T cell response was not major histocompatibility complex-restricted, although it required antigen-presenting cells and was blocked by addition of antibody specific for the T cell receptor (TCR). Sequence analysis of TCR-gamma and -delta chains of peripheral blood lymphocytes identified two novel TCR-gamma chain constant (Cgamma) regions. It is important that all seven MSP2-specific gammadelta T cell clones used the same one of these novel Cgamma regions. The TCR complementarity-determining region 3 was less conserved than those of MSP2-specific CD4+ alphabeta T cell clones. Together, these data indicate that WC1+ gammadelta T cells recognize A. marginale MSP2 through the TCR and contribute to the immunodominant response to this protein.","is_dataset_classified":null,"base_score":4.060443010546419,"endowment":4.060443010546419,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"15522917","pmcid":null,"openalex_id":"https://openalex.org/W1997163103","authors":[],"funders":[{"funder_name":"USDA National Research Initiative Competitive Grants Program","grant_id":"00-52100-9612","title":null},{"funder_name":"NIH National Institute of Allergy and Infectious Diseases","grant_id":"R01-AI44005","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"K08-AI53594","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"T32 AI007025","title":null}],"total_grants":4,"fwci":1.9085,"citation_percentile":0.83976494,"influential_citations":0,"citation_trend":[{"year":2012,"count":4},{"year":2013,"count":2},{"year":2014,"count":6},{"year":2015,"count":4},{"year":2016,"count":3},{"year":2018,"count":3},{"year":2019,"count":2},{"year":2020,"count":4},{"year":2021,"count":7},{"year":2022,"count":2},{"year":2025,"count":3},{"year":2026,"count":1}],"oa_status":"bronze","license":null,"oa_locations":[{"url":"https://academic.oup.com/jleukbio/article-pdf/77/2/199/48549402/jlb0199.pdf","host_type":"journal"},{"url":"https://academic.oup.com/jleukbio/article-pdf/77/2/199/48549402/jlb0199.pdf","host_type":"publisher"},{"url":"https://doi.org/10.1189/jlb.0804482","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/15522917","host_type":"repository"}],"fields_of_study":["Vector-borne infectious diseases","Vector-Borne Animal Diseases","Toxin Mechanisms and Immunotoxins"],"mesh_terms":["Animals","Antigens, Bacterial","Bacterial Outer Membrane Proteins","Cattle","Clone Cells","Molecular Sequence Data","Sequence Homology, Nucleic Acid","CD4-Positive T-Lymphocytes","T-Lymphocyte Subsets","Receptors, Antigen, T-Cell, gamma-delta","Sequence Homology, Amino Acid","Anaplasma marginale"],"keywords":["Biology","T-cell receptor","T cell","Immunodominance","Epitope","Antigen","T lymphocyte","Molecular biology","Virology","Cytotoxic T cell","Immunology","Immune system","Genetics","In vitro"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-05T15:07:50.157463Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}